Connective tissue diseases (CTDs) are Autoimmune diseases (AIDs) characterized by the appearance of autoantibodies, which are diagnostic markers. Investigations of these autoantibodies play a major role in the managem...Connective tissue diseases (CTDs) are Autoimmune diseases (AIDs) characterized by the appearance of autoantibodies, which are diagnostic markers. Investigations of these autoantibodies play a major role in the management of several autoimmune diseases. The objective of this study was to describe the profile of anti-ENA antibodies according to the clinical symptoms of mixed CTDs in Conakry teaching Hospital. We performed a cross-sectional study during six months. A total of 20 patients was recruited and we measured antibodies using the ELISA technique. The mean age of our patients was 36.5 years, with a predominance of females. Cutaneous and rheumatological signs were the main clinical manifestations. SLP was the most frequent CTDs;the threshold of ENA antibodies positivity was higher in scleroderma with and SLP. Anti-ENA identification reveals the frequency of anti-SSA (83.33%), anti-U1RNP (66.66%) and anti-histone (50%) antibodies. Antinuclear antibodies (ANA) react with various components of the cell nucleus. Their detection is of major interest in the diagnosis of CTDs. Our results highlight the importance of determining the specificity of these antibodies to guide differential diagnosis.展开更多
BACKGROUND Primary biliary cholangitis(PBC)is a chronic progressive autoimmune cholestatic disease.The main target organ of PBC is the liver,and nonsuppurative inflammation of the small intrahepatic bile ducts may eve...BACKGROUND Primary biliary cholangitis(PBC)is a chronic progressive autoimmune cholestatic disease.The main target organ of PBC is the liver,and nonsuppurative inflammation of the small intrahepatic bile ducts may eventually develop into cirrhosis or liver fibrosis.AIM To explore the clinical characteristics of early-stage PBC,identify PBC in the early clinical stage,and promptly treat and monitor PBC.METHODS The data of 82 patients with PBC confirmed by pathology at Tianjin Second People’s Hospital from January 2013 to November 2021 were collected,and the patients were divided into stage I,stage II,stage III,and stage IV according to the pathological stage.The general data,serum biochemistry,immunoglobulins,and autoimmune antibodies of patients in each stage were retrospectively analyzed.RESULTS In early-stage(stages I+II)PBC patients,50.0%of patients had normal alanine aminotransferase(ALT)levels,and 37.5%had normal aspartate aminotransferase(AST)levels.For the remaining patients,the ALT and AST levels were mildly elevated;all of these patients had levels of<3 times the upper limit of normal values.The AST levels were significantly different among the three groups(stages I+II vs stage III vs stage IV,P<0.05).In the early stage,29.2%of patients had normal alkaline phosphatase(ALP)levels.The remaining patients had different degrees of ALP elevation;6.3%had ALP levels>5 times the upper limit of normal value.Moreover,γ-glutamyl transferase(GGT)was more robustly elevated,as 29.2%of patients had GGT levels of>10 times the upper limit of normal value.The ALP values among the three groups were significantly different(P<0.05).In early stage,the jaundice index did not increase significantly,but it gradually increased with disease progression.However,the above indicators were significantly different(P<0.05)between the early-stage group and the stage IV group.With the progression of the disease,the levels of albumin and albumin/globulin ratio tended to decrease,and the difference among the three groups was statistically significant(P<0.05).In early-stage patients,IgM and IgG levels as well as cholesterol levels were mildly elevated,but there were no significant differences among the three groups.Triglyceride levels were normal in the early-stage group,and the differences among the three groups were statistically significant(P<0.05).The early detection rates of anti-mitochondria antibody(AMA)and AMA-M2 were 66.7%and 45.8%,respectively.The positive rate of anti-sp100 antibodies was significantly higher in patients with stage IV PBC.When AMA and AMA-M2 were negative,in the early stage,the highest autoantibody was anti-nuclear antibody(ANA)(92.3%),and in all ANA patterns,the highest was ANA centromere(38.5%).CONCLUSION In early-stage PBC patients,ALT and AST levels are normal or mildly elevated,GGT and ALP levels are not elevated in parallel,GGT levels are more robustly elevated,and ALP levels are normal in some patients.When AMA and AMA-M2 are negative,ANA especially ANA centromere positivity suggests the possibility of early PBC.Therefore,in the clinic,significantly elevated GGT levels with or without normal ALP levels and with ANA(particularly ANA centromere)positivity(when AMA and AMA-M2 are negative)may indicate the possibility of early PBC.展开更多
BACKGROUND Defective neutrophil regulation in inflammatory bowel disease(IBD)is thought to play an important role in the onset or manifestation of IBD,as it could lead to damage of the intestinal mucosal barrier by th...BACKGROUND Defective neutrophil regulation in inflammatory bowel disease(IBD)is thought to play an important role in the onset or manifestation of IBD,as it could lead to damage of the intestinal mucosal barrier by the infiltration of neutrophils in the inflamed mucosa and the accumulation of pathogens.Like neutrophils in the context of innate immune responses,immunoglobulin A(IgA)as an acquired immune response partakes in the defense of the intestinal epithelium.Under normal conditions,IgA contributes to the elimination of microbes,but in connection with the loss of tolerance to chitinase 3-like 1(CHI3L1)in IBD,IgA could participate in CHI3L1-mediated improved adhesion and invasion of potentially pathogenic microorganisms.The tolerance brake to CHI3L1 and the occurrence of IgA autoantibodies to this particular target,the exact role and underlying mechanisms of CHI3L1 in the pathogenesis of IBD are still unclear.AIM To determine the predictive potential of Ig subtypes of a novel serological marker,anti-CHI3L1 autoantibodies(aCHI3L1)in determining the disease phenotype,therapeutic strategy and long-term disease course in a prospective referral cohort of adult IBD patients.METHODS Sera of 257 Crohn’s disease(CD)and 180 ulcerative colitis(UC)patients from a tertiary IBD referral center of Hungary(Division of Gastroenterology,Department of Internal Medicine,Faculty of Medicine,University of Debrecen)were assayed for IgG,IgA,and secretory IgA(sIgA)type aCHI3L1 by enzyme-linked immunosorbent assay using recombinant CHI3L1,along with 86 healthy controls(HCONT).RESULTS The IgA type was more prevalent in CD than in UC(29.2%vs 11.1%)or HCONT(2.83%;P<0.0001 for both).However,sIgA subtype aCHI3L1 positivity was higher in both CD and UC patients than in HCONT(39.3%and 32.8%vs 4.65%,respectively;P<0.0001).The presence of both IgA and sIgA aCHI3L1 antibodies was associated with colonic involvement(P<0.0001 and P=0.038,respectively)in patients with CD.Complicated disease behavior at sample procurement was associated with aCHI3L1 sIgA positivity(57.1%vs 36.0%,P=0.009).IgA type aCH3L1 was more prevalent in patients with frequent relapse during the disease course in the CD group(46.9%vs 25.7%,P=0.005).In a group of patients with concomitant presence of pure inflammatory luminal disease and colon involvement at the time of diagnosis,positivity for IgA or sIgA type aCH3L1 predicted faster progression towards a complicated disease course in time-dependent models.This association disappeared after merging subgroups of different disease locations.CONCLUSION CHI3L1 is a novel neutrophil autoantigenic target in IBD.The consideration of antibody classes along with location-based prediction may transform the future of serology in IBD.展开更多
BACKGROUND Several reports of adult-onset immunodeficiency syndrome have been associated with anti-interferon-gamma(IFN-γ)autoantibodies(AIGAs).However,it is rare to find AIGAs with intracranial infections.CASE SUMMA...BACKGROUND Several reports of adult-onset immunodeficiency syndrome have been associated with anti-interferon-gamma(IFN-γ)autoantibodies(AIGAs).However,it is rare to find AIGAs with intracranial infections.CASE SUMMARY In this case study,we report a case of an AIGAs with intracranial infection and hand rashes considered Sweet’s syndrome.The patient presented to our hospital with a persistent cough,a fever that had been going on for 6 mo,and a rash that had been going on for a week.The patient started losing consciousness gradually on the fourth day after admission,with neck stiffness and weakened limb muscles.The upper lobe of the left lung had a high-density mass with no atypia and a few inflammatory cells in the interstitium.Brain magnetic resonance imaging and cerebrospinal fluid suggest intracranial infection.The pathology of the skin damage on the right upper extremity revealed an infectious lesion that was susceptible to Sweet’s disease.It has an anti-IFN-γautoantibody titer of 1:2500.She was given empirical anti-non-tuberculous mycobacterial and antifungal treatments.The patient had no fever,obvious cough,headache,or rash on the hand.She got out of bed and took care of herself following hospitalization and discharge with medicine.CONCLUSION Adults with severe and recurrent infections of several organs should be considered for AIGAs if no other known risk factors exist.AIGAs are susceptible to subsequent intracranial infections and Sweet’s syndrome.展开更多
Primary biliary cirrhosis(PBC)is a chronic progressive cholestatic liver disease characterized by immunemediated destruction of the small-and medium-sized intrahepatic bile ducts and the presence of antimitochondrial ...Primary biliary cirrhosis(PBC)is a chronic progressive cholestatic liver disease characterized by immunemediated destruction of the small-and medium-sized intrahepatic bile ducts and the presence of antimitochondrial antibodies(AMA)in the serum.AMA are detected in over 90%of patients with PBC,whereas their prevalence in the general population is extremely low,varying from 0.16%to 1%.Previous studies have shown that the unique characteristics of biliary epithelial cells undergoing apoptosis may result in a highly direct and very specific immune response to mitochondrial autoantigens.Moreover,recent studies have demonstrated that serum from AMA-positive PBC patients is reactive with a number of xenobiotic modified E2 subunits of the pyruvate dehydrogenase complex,which is not observed in the serum of normal individuals.These findings indicate that chemicals originating from the environment may be associated with a breakdown in the tolerance to mitochondrial autoantigens.While it is currently generally accepted that AMA are the most specific serological markers of PBC,more than 60 au-toantibodies have been investigated in patients with PBC,and some have previously been considered specific to other autoimmune diseases.This review covers the recent progress in research on the pathogenetic and clinical significance of important autoantibodies in PBC.Determining the pathogenic role of those autoantibodies in PBC remains a priority of basic and clinical research.展开更多
AIM: To investigate the prevalence of autoantibodies and their associations with clinical features in Chinesepatients with chronic hepatitis B(CHB).METHODS: A total of 325 Chinese patients with CHB were enrolled in th...AIM: To investigate the prevalence of autoantibodies and their associations with clinical features in Chinesepatients with chronic hepatitis B(CHB).METHODS: A total of 325 Chinese patients with CHB were enrolled in this retrospective,hospitalbased study.Patients with chronic hepatitis C(CHC),autoimmune hepatitis(AIH),or primary biliary cirrhosis(PBC) were included,with healthy donors acting as controls.A panel of autoantibodies that serologically define AIH and PBC was tested by indirect immunofluorescence assay and line immunoassay.The AIH-related autoantibody profile included homogeneous anti-nuclear antibodies(ANA-H),smooth-muscle antibodies,anti-liver kidney microsome type 1,antiliver cytosolic antigen type 1,and anti-soluble liver antigen/liver pancreas; the PBC-related antibodies were characterized by ANA-nuclear dots/membranous rimlike,anti-mitochondrial antibodies-M2(AMA-M2),antiBPO(recombinant antigen targeted by AMA-M2),antiSp100,anti-promyelocytic leukemia protein(anti-PML),and anti-gp210.The dichotomization of clustering was used to unequivocally designate the AIH or PBC profiles for each case.Anti-Ro52 antibodies were also tested.RESULTS: The prevalence of any autoantibody in CHB amounted to 58.2%,which was similar to the 66.2% prevalence in CHC,significantly higher than the 6.7% in the healthy controls(P < 0.001),and lower than the 100% found in AIH and PBC(P = 0.004 and P < 0.001,respectively).There were more anti-PML and anti-gp210 antibodies among the CHB patients than the CHC patients(11.1% vs 0%,P = 0.003; 12.6% vs 0%,P < 0.001,respectively).The prevalence and titer of AMA,anti-BPO,anti-PML,and anti-gp210 were higher in PBC than in those with CHB.Among the CHB patients,the prevalence of ANA,especially ANA-H,was significantly lower in patients with compensated and decompensated cirrhosis compared with patients without cirrhosis.Thirty-eight cases of hepatocellular carcinoma(HCC) in CHB showed a significant differencecompared with non-HCC patients in the prevalence of anti-PML(0% vs 12.5%,P = 0.013).Dichotomization of the autoantibodies revealed that the PBC profile was more prevalent in patients with CHB than in those with CHC,and that it was strongly correlated with both compensated and decompensated cirrhosis.In contrast,the prevalence of the AIH profile was significantly higher in non-cirrhosis patients with CHB than in those with compensated cirrhosis(18.5% vs 8.2%,P = 0.039).Moreover,the AIH profile was also closely associated with hepatitis B e-antigen positivity.CONCLUSION: ANA-H could be an indicator of earlystage CHB.Dichotomizing the autoantibody profiles revealed that the PBC profile is strongly associated with cirrhosis in CHB.展开更多
AIM To investigate the prevalence and clinical significance of autoimmune liver disease(ALD)-related autoantibodies in patients with biliary atresia(BA).METHODS Sera of 124 BA patients and 140 age-matched non-BA contr...AIM To investigate the prevalence and clinical significance of autoimmune liver disease(ALD)-related autoantibodies in patients with biliary atresia(BA).METHODS Sera of 124 BA patients and 140 age-matched non-BA controls were assayed for detection of the following autoantibodies: ALD profile and specific anti-nuclear antibodies(ANAs), by line-blot assay; ANA and antineutrophil cytoplasmic antibody(ANCA), by indirect immunofluorescence assay; specific ANCAs and antiM2-3 E, by enzyme linked immunosorbent assay. Associations of these autoantibodies with the clinical features of BA(i.e., cytomegalovirus infection, degree of liver fibrosis, and short-term prognosis of Kasai procedure) were evaluated by Spearman's correlation coefficient.RESULTS The overall positive rate of serum autoantibodies in preoperative BA patients was 56.5%. ALD profile assay showed that the positive reaction to primary biliary cholangitis-related autoantibodies in BA patients was higher than that to autoimmune hepatitis-related autoantibodies. Among these autoantibodies, anti-BPO was detected more frequently in the BA patients than in the controls(14.8% vs 2.2%, P < 0.05). Accordingly, 32(25.8%) of the 124 BA patients also showed a high positive reaction for anti-M2-3 E. By comparison, the controls had a remarkably lower frequency of anti-M2-3 E(P < 0.05), with 6/92(8.6%) of patients with other liver diseases and 2/48(4.2%) of healthy controls. The prevalence of ANA in BA patients was 11.3%, which was higher than that in disease controls(3.3%, P < 0.05), but the reactivity to specific ANAs was only 8.2%. The prevalence of ANCAs(ANCA or specific ANCAs) in BA patients was also remarkably higher than that in the healthy controls(37.9% vs 6.3%, P < 0.05), but showed no difference from that in patients with other cholestasis. ANCA positivity was closely associated with the occurrence of postoperative cholangitis(r = 0.61, P < 0.05), whereas none of the autoantibodies showed a correlation to cytomegalovirus infection or the stages of liver fibrosis.CONCLUSION High prevalence of autoantibodies in the BA developmental process strongly reveals the autoimmunemediated pathogenesis. Serological ANCA positivity may be a useful predictive biomarker of postoperative cholangitis.展开更多
Immune-driven inflammation plays an important part inatherogenesis and is therefore believed to be key to thedevelopment of cardiovascular disease(CVD), whichis currently the leading cause of death in the Westernworld...Immune-driven inflammation plays an important part inatherogenesis and is therefore believed to be key to thedevelopment of cardiovascular disease(CVD), whichis currently the leading cause of death in the Westernworld. By fulfilling some of the Koch postulates, athero-genesis has even been proposed to be considered as anautoimmune disease, raising the hope that CVD couldbe prevented by immunomodulation. Nevertheless,the role of the immune system and autoimmune reac-tions in atherosclerosis appear to be a double edged-sword, with both pro-atherogenic and anti-atherogenicattributes. Hence, if immunomodulation is to becomea therapeutic option for atherosclerosis and CVD, it willbe crucial to correctly identify patients who might ben-efit from targeted suppression of deleterious autoim-mune responses. This could be achieved, for example, by the detection of disease-associated autoantibodies. In this work, we will review the currently available clini-cal, in vitro, and animal studies dedicated to autoan-tibodies against apolipoprotein A-1(anti-apoA-1 IgG), the major proteic fraction of high density lipoprotein. Current clinical studies indicate that high levels of anti-apoA-1 IgG are associated with a worse cardiovascular prognosis. In addition, in vitro and animal studies indi-cate a pro-inflammatory and pro-atherogenic role, sup-porting the hypothesis that these autoantibodies may play a direct causal role in CVD, and furthermore that they could potentially represent a therapeutic target for CVD in the future.展开更多
BACKGROUND: Chronic hepatitis C virus(HCV) infection is associated with autoimmune phenomena and is often complicated by anemia. Circulating autoantibodies to endogenous erythropoietin(anti-EPO) have been detected in ...BACKGROUND: Chronic hepatitis C virus(HCV) infection is associated with autoimmune phenomena and is often complicated by anemia. Circulating autoantibodies to endogenous erythropoietin(anti-EPO) have been detected in patients with chronic viral infections and were correlated to anemia. The present study aimed to determine anti-EPO prevalence in patients with chronic HCV infection and investigate its possible association with anemia.METHODS: Ninety-three consecutive patients(62 males and 31 females) with chronic HCV infection, who had never received antiviral therapy or recombinant EPO, were enrolled in the study. Circulating anti-EPO were detected in the serum by using an ELISA assay. Quantitative determination of serum EPO levels was done by radioimmunoassay. HCV RNA viral load measurement and genotype sequencing were also performed.RESULTS: Circulating anti-EPO were detected in 10.8% of HCV-infected patients and the prevalence of anti-EPO was significantly higher in patients with anemia(19.4% vs 5.3%, P=0.040) compared to that in those without anemia. Compared to anti-EPO negative cases, anti-EPO positive patients had higher frequency of anemia(70.0% vs 34.9%, P=0.030), lower EPO concentrations(median 16.35 vs 30.65 m U/m L, P=0.005), and higher HCV RNA viral load(median 891.5×103 vs 367.5×103 IU/m L, P=0.016). In multivariate regression analysis the presence of anti-EPO remained an independent predictor of anemia(adjusted OR: 14.303, 95% CI: 1.417-36.580, P=0.024). EPO response to anemia was less prominent among anti-EPO positive patients(P=0.001).CONCLUSIONS: Circulating anti-EPO are detected in a significant proportion of treatment-na?ve HCV-infected patients and are independently associated with anemia, suggesting a further implication of autoimmunity in the pathophysiology of HCV-related anemia.展开更多
AIM: To investigate the presence of autoantibodies directed against liver sinusoidal cells in primary biliary cirrhosis(PBC).METHODS: Liver biopsies from 21 PBC patients were studied and compared with 12 liver biopsie...AIM: To investigate the presence of autoantibodies directed against liver sinusoidal cells in primary biliary cirrhosis(PBC).METHODS: Liver biopsies from 21 PBC patients were studied and compared with 12 liver biopsies from disease controls [3 patients with hepatitis B(HBV) virus,3 patients with hepatitis C virus(HCV), 3 patients with non-alcoholic steatohepatitis and 3 patients with acute alcoholic hepatitis(AAH)]. As healthy controls, we used tissue specimens adjacent to metastatic liver adenocarcinoma. Normal serum was taken from staff members of the unit. The determination of the cell type targetedby autoantibodies present in the patients sera was performed by indirect immunofluorescence(IIF) analysis using paraffin-embedded liver sections as a substrate.Sera from homologous or heterologous PBC patients or sera from the disease control group were used as primary antibodies. The presence of autoantibodies was identified using confocal microscopy.RESULTS: In total, 18/21(85.7%) PBC patients exhibited positive staining in the sinusoidal cells, 10/21(47.6%) in lymphocytes, 8/21(38%) in cholangiocytes and 7/21(33.3%) in hepatocytes, when homologous serum and fluorescein isothiocyanate-conjugated immunoglobulin type G(IgG) secondary antibody were used. PBC sections incubated with heterologous PBC serum showed reduced staining(20% for sinusoidal cells, 20% for lymphocytes, 20% for cholangiocytes and 13.3% for hepatocytes). When IgM immunoglobulin, instead of IgG, was used as secondary antibody,positive staining was observed in 75% of lymphocytes,62.5% of cholangiocytes, 37.5% of hepatocytes and50% of the sinusoidal cells with a much stronger staining intensity. No staining was observed when either normal or PBC sera were used as a primary antibody on liver sections from the disease control group. When PBC sera were incubated with healthy control sections,weak positive staining of cholangiocytes was observed in 3/21(14.3%) PBC serum samples. Steatohepatitis serum on PBC sections gave a positive staining of some hepatocytes and lymphocytes but no staining on viral hepatitis sections. Incubation with HBV sera stained some hepatocytes, cholangiocytes and intra-sinusoidal or portal lymphocytes of PBC, HBV and AAH patients but not HCV patients.CONCLUSION: In this study, for the first time in diseased liver tissue, we have demonstrated that a large proportion of PBC patients have disease specific autoantibodies against liver sinusoidal cells.展开更多
Objective To determine the possible association of anti-β1-adrenergic receptors(anti-β1-AR), anti-β2-AR and anti-α1-AR with carvedilol treatment in patients with heart failure(HF). Methods A total of 267 HF patien...Objective To determine the possible association of anti-β1-adrenergic receptors(anti-β1-AR), anti-β2-AR and anti-α1-AR with carvedilol treatment in patients with heart failure(HF). Methods A total of 267 HF patients were prospectively enrolled. Blood samples were measured by an enzyme-linked immunosorbent assay. All of the patients received carvedilol for their HF. Each patient was followed up for six months and their cardiac function was measured. Results The final analysis encompassed 137 patients comprising 65 patients with three autoantibodies(positive group) and 72 patients without all three autoantibodies but with one or two autoantibodies(negative group). The frequency and geometric mean titer of anti-β1-AR, anti-β2-AR, and anti-α1-AR were significantly lower in the group without all three autoantibodies after six months of carvedilol treatment(all P < 0.01;from 100% to 57%, 50%, and 49%, respectively;and from 1: 118, 1: 138, and 1: 130 to 1: 72, 1: 61, and 1: 67, respectively). Furthermore, 28 patients in the positive group demonstrated complete ablation of autoantibodies. In addition, left ventricular remodelling and function was significantly improved by the use of carvedilol combined with the standard treatment regime for six months in the positive group(P < 0.01) when compared to the negative group(P < 0.05). Conclusions Carvedilol treatment significantly decreases frequency and geometric mean titer in patients with all three autoantibodies, even up to complete ablation, and significantly improved cardiac function and remodelling. The effect of carvedilol is probably correlated to the presence of all three autoantibodies.展开更多
We have previously reported the high levels of glutamic acid decarboxylase 65 autoantibodies(GAD65A)in patients with type 1 diabetes and autoimmune thyroid disease.Here we describe a 32-year-old Japanese female with a...We have previously reported the high levels of glutamic acid decarboxylase 65 autoantibodies(GAD65A)in patients with type 1 diabetes and autoimmune thyroid disease.Here we describe a 32-year-old Japanese female with a thirteen-year history of type 1 diabetes whose levels of GAD65A were elevated just after the emergence of anti-thyroid autoimmunity.At 19 years of age,she developed diabetic ketoacidosis and was diagnosed with type 1 diabetes.She had GAD65A,insulinoma-associated antigen-2 autoantibodies(IA-2A),and zinc transporter-8 autoantibodies(ZnT8A),but was negative for antibodies to thyroid peroxidase(TPOAb)and thyroglobulin(TGAb)at disease onset.ZnT8A and IA-2A turned negative 2-3 years after the onset,whereas GAD65A were persistently positive at lower level(approximately 40 U/mL).However,just after the emergence of TGAb at disease duration of 12.5 years,GAD65A levels were reelevated up to5717 U/mL in the absence of ZnT8A and IA-2A.Her thyroid function was normal and TPOAb were consistently negative.She has a HLA-DRB1*03:01/*04:01-DQB1*02:01/*03:02 genotype.Persistent positivity for GAD65A might be associated with increased risk to develop anti-thyroid autoimmunity.展开更多
OBJECTIVE: To develope a new enzyme immune assay (ELISA) for detection of M2 antibody specificfor primary biliary cirrhosis (PBC) by using a triple hybrid clone as antigen, which coexpresses the threeimmunodominant li...OBJECTIVE: To develope a new enzyme immune assay (ELISA) for detection of M2 antibody specificfor primary biliary cirrhosis (PBC) by using a triple hybrid clone as antigen, which coexpresses the threeimmunodominant lipoyl domains of PDC-E2, BCOADC-E2 and OGDC-E2 from human sources.METHODS: After expressing autoantigens of PBC in prokaryote by constructing recombinant expressiveplasmid successfully, the fusion protein was purified by affinity chromatography. The sera of 17 PBCpatients were examined. As controls, the sera of 167 non-PBC patients and the sera of 1225 normalcontrols aged under 28 were examined.RESULTS: None of the sera from the non-PBC patients or the normal controls was positive for anti-M2shown by the new ELISA. However, the positivity rate for anti-M2 in the PBC patients was 100%(17/17), as shown by the new ELISA.CONCLUSION: The detection system with a good sensitivity and specificity may be used as a powerfulmethod for the diagnosis of PBC.展开更多
Colorectal cancer(CRC)is the second leading cause of cancer-related death worldwide.The five-year survival rate of CRC patients depends on the stage at diagnosis,being higher than 80%when CRC is diagnosed in the early...Colorectal cancer(CRC)is the second leading cause of cancer-related death worldwide.The five-year survival rate of CRC patients depends on the stage at diagnosis,being higher than 80%when CRC is diagnosed in the early stages but lower than 10%when CRC is diagnosed in advanced stages.Autoantibodies against specific CRC autoantigens(tumor-associated antigens(TAAs))in the sera of patients have been widely demonstrated to aid in early diagnosis.Thus,we herein aim to identify autoantigens target of autoantibodies specific to CRC that possess a significant ability to discriminate between CRC patients and healthy individuals by means of liquid biopsy.To that end,we examined the protein content of the exosomes released by five CRC cell lines and tissue samples from CRC patients by means of immunoprecipitation coupled with mass spectrometry analysis.A total of 103 proteins were identified as potential autoantigens specific to CRC.After bioinformatics and meta-analysis,we selected 15 proteins that are more likely to be actual CRC autoantigens in order to evaluate their role in CRC prognosis by Western blot(WB)and immunohistochemistry(IHC).We found dysregulation at the protein level for 11 of these proteins in both tissue and plasma exosome samples from patients,along with an association of nine of these proteins with CRC prognosis.After validation,all but one showed a statistically significant high diagnostic ability to distinguish CRC patients and individuals with premalignant lesions from healthy individuals,either by luminescence Halotag-based beads,or by a multiplexed biosensing platform involving the use of magnetic microcarriers as solid support modified with covalently immobilized Halotag fusion proteins constructed for CRC detection.Taken together,our results highlight the usefulness of the approach defined here to identify the TAAs specific to chronic diseases;they also demonstrate that the measurement of autoantibody levels in plasma against the TAAs identified here could be integrated into a point-of-care(POC)device for CRC detection with high diagnostic ability.展开更多
Aim: To determine the clinical and immunological characteristics of patients with systemic erythematosus lupus in Abidjan. Patients and Method: We studied 117 patients’ files with systemic lupus erythematosus aged 12...Aim: To determine the clinical and immunological characteristics of patients with systemic erythematosus lupus in Abidjan. Patients and Method: We studied 117 patients’ files with systemic lupus erythematosus aged 12 to 73 years old, who fulfilled the American College of Rheumatology (ACR)’s criteria. Antinuclear autoantibodies (ANA) were searched by indirect immunofluorescence. Anti-DNA native autoantibodies, extractable nuclear anti-antigens autoantibodies (anti-Sm, anti-SSA, anti-SSB and anti-RNP) and anti-phospholipids autoantibodies have been searched by ELISA technic. Results: The most frequent clinical manifestations were: articular damages (86.32%), cutaneous and mucosal lesions (71.79%) and fever (76.67%). Kidney damages have been noticed in 40.17%. Neurologic manifestations have been observed in 36.75%. Pericarditis and pleurisies have been noticed in 22.22% and 11.97% of cases, and anaemia in 86.32% of cases. ANA have been detected in 94.12% of cases, anti-DNA native’s autoantibodies in 73.53% and anti-Sm autoantibodies in 75% of cases. Anti-SSA and anti-SSB autoantibodies were respectively in 75% and 56.25% of cases. Anti-RNP autoantibodies were in all the patients, and anti-phospholipids autoantibodies were in 37.50% of cases. Conclusion: Systemic lupus erythematosus of Ivorian black subject is characterised by high prevalence of autoantibodies, mostly Anti-RNP.展开更多
We have studied the level of autoantibodies to neurospecific proteins and neurotransmitters in patients with different forms of ischemic brain lesion. 49 patients with acute (ishemic stroke) and chronic cerebrovascula...We have studied the level of autoantibodies to neurospecific proteins and neurotransmitters in patients with different forms of ischemic brain lesion. 49 patients with acute (ishemic stroke) and chronic cerebrovascular disease, 14 patients with ishemic heart disease and control group (35 healthy subjects) were investigated. The serum level of autoantibodies to glial fibrillary acidic protein (GFAP) and to dopamine (D) was determinated by ELISA. The content of autoantibodies to GFAP and D in patients with ischemic heart disease was practically identical. The patients with acute and chronic cerebrovas-cular diseases had the significally increased level of autoantibodies. The level of autoantibodies to GFAP in patients with acute vascular accidents (ischemic stroke) with favorable outcome was significantly higher than in patients with chronic cerebral ischemia. The obtained data allowed us to consider serum level of autoantibodies to GFAP as a marker of ischemic brain lesion, and to suppose further potential role of this autoantibodies in cerebrovascular disease progression.展开更多
Background: Low-dose computed tomography (CT) screening reduces lung cancer mortality but costs are prohibitive for most healthcare budgets due to high false positive rates. An adjunctive test able to distinguish mali...Background: Low-dose computed tomography (CT) screening reduces lung cancer mortality but costs are prohibitive for most healthcare budgets due to high false positive rates. An adjunctive test able to distinguish malignant from benign pulmonary nodules would be hugely beneficial. EarlyCDT-Lung measures serum autoantibodies to tumor-associated antigens and has found clinical acceptance to aid early detection of lung cancer for high risk patients. However performance was optimized for screening. The construction of a receiver-operating characteristic (ROC) curve would enable optimization of performance for alternative settings, including nodule malignancy. Methods: A Monte-Carlo search method was used to construct a ROC curve using a case-control cohort, enabling high and low specificity versions of EarlyCDT-Lung to be determined. These were used for a theoretical evaluation of a nodule cohort, and positive predictive value (PPV) was calculated under the assumption of independence of risk source. Patients or their nodules are typically classified into three risk groups: low (0% - 10%), intermediate (10% - 65%) and high (>65%) risk of malignancy. The predicted shift in risk group by application of the high and low specificity versions, along with the current commercial EarlyCDT-Lung, was then estimated. Results: The ROC curve, with an area under the curve of 0.743, was constructed. The high specificity (98%), low specificity (49%) and current commercial (91% specificity) versions of EarlyCDT-Lung re-classified 27%, 23% and 26% of intermediate nodules, respectively, to either a higher (10%, 8% and 10%) or lower (17%, 15% and 16%) risk group. Conclusion: A ROC curve was constructed to allow performance prediction of EarlyCDT-Lung at different specificities in the indeterminate nodule setting. This enabled risk re-classification of intermediate risk nodules, and could therefore facilitate alternative more appropriate intervention. We have shown how a multivariate biomarker test can add to the interpretation of pulmonary nodules and therefore aid patient management.展开更多
Background: We wanted to determine (via an immunopharmacological approach) whether the c-Jun NH2 terminal kinase (JNK) cascade is phosphorylated in the submandibular gland by carbachol and cholinergic autoantibodies (...Background: We wanted to determine (via an immunopharmacological approach) whether the c-Jun NH2 terminal kinase (JNK) cascade is phosphorylated in the submandibular gland by carbachol and cholinergic autoantibodies (IgG) present in the sera of patients with primary Sj?gren’s syndrome (pSS) by interaction and activation of salivary gland muscarinic acetylcholine receptors (mAChRs). Methods: The JNK, PGE2 and NOS assays were measured in rat sub- mandibular gland with pSS IgG and carbachol alone or in the presence of different blocker agents. Results: pSS IgG- activated M3 mAChRs stimulated JNK phosphorylation whereas the activation of M1 mAChRs by carbachol stimulated JNK phosphorylation involving calcium-activated mechanism. The intracellular pathway leading to pSS IgG-induced biological effects on JNK activity involved activation of protein kinase C (PKC), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) enzymes. Also, activation of COX-2 and COX-1 by pSS IgG and carbachol-induced PGE2 generation were involved. Conclusion: These results may contribute to better understanding the modulatory role of JNK enzymes by cholinergic autoantibodies from pSS patients acting on mAChR in rat submandibular gland.展开更多
Background: Type 1 Diabetes mellitus (T1DM) results from a cellular-mediated autoimmune destruction of the β-cells of the pancreas. We designed this study to determine the prevalence of autoantibodies among Saudis pa...Background: Type 1 Diabetes mellitus (T1DM) results from a cellular-mediated autoimmune destruction of the β-cells of the pancreas. We designed this study to determine the prevalence of autoantibodies among Saudis patients with T1DM. Methods: Glutamic acid decarboxylase antibodies (GADA), antibodies to Islet cell (ICA) and Insulin (IAA) were measured in 171 Saudis patients with T1DM. Results: There were 171 patients with T1DM, 71 males (41.5%) and 100 females (58.5%). The mean age was 20.8 ± 6.6 and the mean diabetes duration was 7.7 ± 5.7. GADA, ICA and IAA were detected in 53.8%, 32.2% and 76% respectively. GADA, ICA and IAA were nonsignificantly more frequent in female and GADA and IAA were significantly more frequent in those younger than 20 years of age. Subjects testing positive for GADA had higher levels of ICA (42.4% vs. 20.3, p = 0.003) and IAA (79.3% vs. 72.2, p = 0.3) than those negative for GADA. Multiple antibodies (≥2) were observed more often in patients under the age of 20 years. There were nonsignificant differences in the prevalence of multiple antibodies between both genders. Multiple logistic regression analysis showed a significant independent positive relationship between the serum positivity of GADA, ICA and Multiple antibodies (≥2) with diabetes duration (0.02, p = 0.03, 0.02, p = 0.01 and 0.01, p = 0.04 respectively). Conclusions: The prevalence of autoantibodies in Saudi patients with T1DM is similar to those reported for diabetic patients in other ethnic groups.展开更多
文摘Connective tissue diseases (CTDs) are Autoimmune diseases (AIDs) characterized by the appearance of autoantibodies, which are diagnostic markers. Investigations of these autoantibodies play a major role in the management of several autoimmune diseases. The objective of this study was to describe the profile of anti-ENA antibodies according to the clinical symptoms of mixed CTDs in Conakry teaching Hospital. We performed a cross-sectional study during six months. A total of 20 patients was recruited and we measured antibodies using the ELISA technique. The mean age of our patients was 36.5 years, with a predominance of females. Cutaneous and rheumatological signs were the main clinical manifestations. SLP was the most frequent CTDs;the threshold of ENA antibodies positivity was higher in scleroderma with and SLP. Anti-ENA identification reveals the frequency of anti-SSA (83.33%), anti-U1RNP (66.66%) and anti-histone (50%) antibodies. Antinuclear antibodies (ANA) react with various components of the cell nucleus. Their detection is of major interest in the diagnosis of CTDs. Our results highlight the importance of determining the specificity of these antibodies to guide differential diagnosis.
文摘BACKGROUND Primary biliary cholangitis(PBC)is a chronic progressive autoimmune cholestatic disease.The main target organ of PBC is the liver,and nonsuppurative inflammation of the small intrahepatic bile ducts may eventually develop into cirrhosis or liver fibrosis.AIM To explore the clinical characteristics of early-stage PBC,identify PBC in the early clinical stage,and promptly treat and monitor PBC.METHODS The data of 82 patients with PBC confirmed by pathology at Tianjin Second People’s Hospital from January 2013 to November 2021 were collected,and the patients were divided into stage I,stage II,stage III,and stage IV according to the pathological stage.The general data,serum biochemistry,immunoglobulins,and autoimmune antibodies of patients in each stage were retrospectively analyzed.RESULTS In early-stage(stages I+II)PBC patients,50.0%of patients had normal alanine aminotransferase(ALT)levels,and 37.5%had normal aspartate aminotransferase(AST)levels.For the remaining patients,the ALT and AST levels were mildly elevated;all of these patients had levels of<3 times the upper limit of normal values.The AST levels were significantly different among the three groups(stages I+II vs stage III vs stage IV,P<0.05).In the early stage,29.2%of patients had normal alkaline phosphatase(ALP)levels.The remaining patients had different degrees of ALP elevation;6.3%had ALP levels>5 times the upper limit of normal value.Moreover,γ-glutamyl transferase(GGT)was more robustly elevated,as 29.2%of patients had GGT levels of>10 times the upper limit of normal value.The ALP values among the three groups were significantly different(P<0.05).In early stage,the jaundice index did not increase significantly,but it gradually increased with disease progression.However,the above indicators were significantly different(P<0.05)between the early-stage group and the stage IV group.With the progression of the disease,the levels of albumin and albumin/globulin ratio tended to decrease,and the difference among the three groups was statistically significant(P<0.05).In early-stage patients,IgM and IgG levels as well as cholesterol levels were mildly elevated,but there were no significant differences among the three groups.Triglyceride levels were normal in the early-stage group,and the differences among the three groups were statistically significant(P<0.05).The early detection rates of anti-mitochondria antibody(AMA)and AMA-M2 were 66.7%and 45.8%,respectively.The positive rate of anti-sp100 antibodies was significantly higher in patients with stage IV PBC.When AMA and AMA-M2 were negative,in the early stage,the highest autoantibody was anti-nuclear antibody(ANA)(92.3%),and in all ANA patterns,the highest was ANA centromere(38.5%).CONCLUSION In early-stage PBC patients,ALT and AST levels are normal or mildly elevated,GGT and ALP levels are not elevated in parallel,GGT levels are more robustly elevated,and ALP levels are normal in some patients.When AMA and AMA-M2 are negative,ANA especially ANA centromere positivity suggests the possibility of early PBC.Therefore,in the clinic,significantly elevated GGT levels with or without normal ALP levels and with ANA(particularly ANA centromere)positivity(when AMA and AMA-M2 are negative)may indicate the possibility of early PBC.
基金Supported by the German Federal Ministry of Education and Research(BMBF-Wachstumskern-PRAEMED.BIO),03WKDB2Csupported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences,BO/00232/17/5+1 种基金Research Grants of National Research Development and Innovation Office,K115818/2015/1New National Excellence Program of the Ministry of Human Capacities,ÚNKP-18-4 Bolyai Plus.
文摘BACKGROUND Defective neutrophil regulation in inflammatory bowel disease(IBD)is thought to play an important role in the onset or manifestation of IBD,as it could lead to damage of the intestinal mucosal barrier by the infiltration of neutrophils in the inflamed mucosa and the accumulation of pathogens.Like neutrophils in the context of innate immune responses,immunoglobulin A(IgA)as an acquired immune response partakes in the defense of the intestinal epithelium.Under normal conditions,IgA contributes to the elimination of microbes,but in connection with the loss of tolerance to chitinase 3-like 1(CHI3L1)in IBD,IgA could participate in CHI3L1-mediated improved adhesion and invasion of potentially pathogenic microorganisms.The tolerance brake to CHI3L1 and the occurrence of IgA autoantibodies to this particular target,the exact role and underlying mechanisms of CHI3L1 in the pathogenesis of IBD are still unclear.AIM To determine the predictive potential of Ig subtypes of a novel serological marker,anti-CHI3L1 autoantibodies(aCHI3L1)in determining the disease phenotype,therapeutic strategy and long-term disease course in a prospective referral cohort of adult IBD patients.METHODS Sera of 257 Crohn’s disease(CD)and 180 ulcerative colitis(UC)patients from a tertiary IBD referral center of Hungary(Division of Gastroenterology,Department of Internal Medicine,Faculty of Medicine,University of Debrecen)were assayed for IgG,IgA,and secretory IgA(sIgA)type aCHI3L1 by enzyme-linked immunosorbent assay using recombinant CHI3L1,along with 86 healthy controls(HCONT).RESULTS The IgA type was more prevalent in CD than in UC(29.2%vs 11.1%)or HCONT(2.83%;P<0.0001 for both).However,sIgA subtype aCHI3L1 positivity was higher in both CD and UC patients than in HCONT(39.3%and 32.8%vs 4.65%,respectively;P<0.0001).The presence of both IgA and sIgA aCHI3L1 antibodies was associated with colonic involvement(P<0.0001 and P=0.038,respectively)in patients with CD.Complicated disease behavior at sample procurement was associated with aCHI3L1 sIgA positivity(57.1%vs 36.0%,P=0.009).IgA type aCH3L1 was more prevalent in patients with frequent relapse during the disease course in the CD group(46.9%vs 25.7%,P=0.005).In a group of patients with concomitant presence of pure inflammatory luminal disease and colon involvement at the time of diagnosis,positivity for IgA or sIgA type aCH3L1 predicted faster progression towards a complicated disease course in time-dependent models.This association disappeared after merging subgroups of different disease locations.CONCLUSION CHI3L1 is a novel neutrophil autoantigenic target in IBD.The consideration of antibody classes along with location-based prediction may transform the future of serology in IBD.
基金2020 Guangxi University Young and Middle aged Teachers'Basic Research Ability Improvement Project,No.2020KY03032.
文摘BACKGROUND Several reports of adult-onset immunodeficiency syndrome have been associated with anti-interferon-gamma(IFN-γ)autoantibodies(AIGAs).However,it is rare to find AIGAs with intracranial infections.CASE SUMMARY In this case study,we report a case of an AIGAs with intracranial infection and hand rashes considered Sweet’s syndrome.The patient presented to our hospital with a persistent cough,a fever that had been going on for 6 mo,and a rash that had been going on for a week.The patient started losing consciousness gradually on the fourth day after admission,with neck stiffness and weakened limb muscles.The upper lobe of the left lung had a high-density mass with no atypia and a few inflammatory cells in the interstitium.Brain magnetic resonance imaging and cerebrospinal fluid suggest intracranial infection.The pathology of the skin damage on the right upper extremity revealed an infectious lesion that was susceptible to Sweet’s disease.It has an anti-IFN-γautoantibody titer of 1:2500.She was given empirical anti-non-tuberculous mycobacterial and antifungal treatments.The patient had no fever,obvious cough,headache,or rash on the hand.She got out of bed and took care of herself following hospitalization and discharge with medicine.CONCLUSION Adults with severe and recurrent infections of several organs should be considered for AIGAs if no other known risk factors exist.AIGAs are susceptible to subsequent intracranial infections and Sweet’s syndrome.
文摘Primary biliary cirrhosis(PBC)is a chronic progressive cholestatic liver disease characterized by immunemediated destruction of the small-and medium-sized intrahepatic bile ducts and the presence of antimitochondrial antibodies(AMA)in the serum.AMA are detected in over 90%of patients with PBC,whereas their prevalence in the general population is extremely low,varying from 0.16%to 1%.Previous studies have shown that the unique characteristics of biliary epithelial cells undergoing apoptosis may result in a highly direct and very specific immune response to mitochondrial autoantigens.Moreover,recent studies have demonstrated that serum from AMA-positive PBC patients is reactive with a number of xenobiotic modified E2 subunits of the pyruvate dehydrogenase complex,which is not observed in the serum of normal individuals.These findings indicate that chemicals originating from the environment may be associated with a breakdown in the tolerance to mitochondrial autoantigens.While it is currently generally accepted that AMA are the most specific serological markers of PBC,more than 60 au-toantibodies have been investigated in patients with PBC,and some have previously been considered specific to other autoimmune diseases.This review covers the recent progress in research on the pathogenetic and clinical significance of important autoantibodies in PBC.Determining the pathogenic role of those autoantibodies in PBC remains a priority of basic and clinical research.
文摘AIM: To investigate the prevalence of autoantibodies and their associations with clinical features in Chinesepatients with chronic hepatitis B(CHB).METHODS: A total of 325 Chinese patients with CHB were enrolled in this retrospective,hospitalbased study.Patients with chronic hepatitis C(CHC),autoimmune hepatitis(AIH),or primary biliary cirrhosis(PBC) were included,with healthy donors acting as controls.A panel of autoantibodies that serologically define AIH and PBC was tested by indirect immunofluorescence assay and line immunoassay.The AIH-related autoantibody profile included homogeneous anti-nuclear antibodies(ANA-H),smooth-muscle antibodies,anti-liver kidney microsome type 1,antiliver cytosolic antigen type 1,and anti-soluble liver antigen/liver pancreas; the PBC-related antibodies were characterized by ANA-nuclear dots/membranous rimlike,anti-mitochondrial antibodies-M2(AMA-M2),antiBPO(recombinant antigen targeted by AMA-M2),antiSp100,anti-promyelocytic leukemia protein(anti-PML),and anti-gp210.The dichotomization of clustering was used to unequivocally designate the AIH or PBC profiles for each case.Anti-Ro52 antibodies were also tested.RESULTS: The prevalence of any autoantibody in CHB amounted to 58.2%,which was similar to the 66.2% prevalence in CHC,significantly higher than the 6.7% in the healthy controls(P < 0.001),and lower than the 100% found in AIH and PBC(P = 0.004 and P < 0.001,respectively).There were more anti-PML and anti-gp210 antibodies among the CHB patients than the CHC patients(11.1% vs 0%,P = 0.003; 12.6% vs 0%,P < 0.001,respectively).The prevalence and titer of AMA,anti-BPO,anti-PML,and anti-gp210 were higher in PBC than in those with CHB.Among the CHB patients,the prevalence of ANA,especially ANA-H,was significantly lower in patients with compensated and decompensated cirrhosis compared with patients without cirrhosis.Thirty-eight cases of hepatocellular carcinoma(HCC) in CHB showed a significant differencecompared with non-HCC patients in the prevalence of anti-PML(0% vs 12.5%,P = 0.013).Dichotomization of the autoantibodies revealed that the PBC profile was more prevalent in patients with CHB than in those with CHC,and that it was strongly correlated with both compensated and decompensated cirrhosis.In contrast,the prevalence of the AIH profile was significantly higher in non-cirrhosis patients with CHB than in those with compensated cirrhosis(18.5% vs 8.2%,P = 0.039).Moreover,the AIH profile was also closely associated with hepatitis B e-antigen positivity.CONCLUSION: ANA-H could be an indicator of earlystage CHB.Dichotomizing the autoantibody profiles revealed that the PBC profile is strongly associated with cirrhosis in CHB.
基金the Guangdong Provincial Science and Technology Planning Project,No.2014A020212520the Guangzhou Science and Technology Project,No.201707010014
文摘AIM To investigate the prevalence and clinical significance of autoimmune liver disease(ALD)-related autoantibodies in patients with biliary atresia(BA).METHODS Sera of 124 BA patients and 140 age-matched non-BA controls were assayed for detection of the following autoantibodies: ALD profile and specific anti-nuclear antibodies(ANAs), by line-blot assay; ANA and antineutrophil cytoplasmic antibody(ANCA), by indirect immunofluorescence assay; specific ANCAs and antiM2-3 E, by enzyme linked immunosorbent assay. Associations of these autoantibodies with the clinical features of BA(i.e., cytomegalovirus infection, degree of liver fibrosis, and short-term prognosis of Kasai procedure) were evaluated by Spearman's correlation coefficient.RESULTS The overall positive rate of serum autoantibodies in preoperative BA patients was 56.5%. ALD profile assay showed that the positive reaction to primary biliary cholangitis-related autoantibodies in BA patients was higher than that to autoimmune hepatitis-related autoantibodies. Among these autoantibodies, anti-BPO was detected more frequently in the BA patients than in the controls(14.8% vs 2.2%, P < 0.05). Accordingly, 32(25.8%) of the 124 BA patients also showed a high positive reaction for anti-M2-3 E. By comparison, the controls had a remarkably lower frequency of anti-M2-3 E(P < 0.05), with 6/92(8.6%) of patients with other liver diseases and 2/48(4.2%) of healthy controls. The prevalence of ANA in BA patients was 11.3%, which was higher than that in disease controls(3.3%, P < 0.05), but the reactivity to specific ANAs was only 8.2%. The prevalence of ANCAs(ANCA or specific ANCAs) in BA patients was also remarkably higher than that in the healthy controls(37.9% vs 6.3%, P < 0.05), but showed no difference from that in patients with other cholestasis. ANCA positivity was closely associated with the occurrence of postoperative cholangitis(r = 0.61, P < 0.05), whereas none of the autoantibodies showed a correlation to cytomegalovirus infection or the stages of liver fibrosis.CONCLUSION High prevalence of autoantibodies in the BA developmental process strongly reveals the autoimmunemediated pathogenesis. Serological ANCA positivity may be a useful predictive biomarker of postoperative cholangitis.
基金Supported by Swiss National Science Foundation Grants to Dr.Vuilleumier N No.310030_140736and to Dr.Montecucco F No.32003B_134963/1a grant from the Foundation"Gustave and Simone Prévot"to Dr.Montecucco F
文摘Immune-driven inflammation plays an important part inatherogenesis and is therefore believed to be key to thedevelopment of cardiovascular disease(CVD), whichis currently the leading cause of death in the Westernworld. By fulfilling some of the Koch postulates, athero-genesis has even been proposed to be considered as anautoimmune disease, raising the hope that CVD couldbe prevented by immunomodulation. Nevertheless,the role of the immune system and autoimmune reac-tions in atherosclerosis appear to be a double edged-sword, with both pro-atherogenic and anti-atherogenicattributes. Hence, if immunomodulation is to becomea therapeutic option for atherosclerosis and CVD, it willbe crucial to correctly identify patients who might ben-efit from targeted suppression of deleterious autoim-mune responses. This could be achieved, for example, by the detection of disease-associated autoantibodies. In this work, we will review the currently available clini-cal, in vitro, and animal studies dedicated to autoan-tibodies against apolipoprotein A-1(anti-apoA-1 IgG), the major proteic fraction of high density lipoprotein. Current clinical studies indicate that high levels of anti-apoA-1 IgG are associated with a worse cardiovascular prognosis. In addition, in vitro and animal studies indi-cate a pro-inflammatory and pro-atherogenic role, sup-porting the hypothesis that these autoantibodies may play a direct causal role in CVD, and furthermore that they could potentially represent a therapeutic target for CVD in the future.
基金supported by a grant from the Special Account for Research Grants(ELKE)of the National and Kapodistrian University of Athens(No.70/3/7247)
文摘BACKGROUND: Chronic hepatitis C virus(HCV) infection is associated with autoimmune phenomena and is often complicated by anemia. Circulating autoantibodies to endogenous erythropoietin(anti-EPO) have been detected in patients with chronic viral infections and were correlated to anemia. The present study aimed to determine anti-EPO prevalence in patients with chronic HCV infection and investigate its possible association with anemia.METHODS: Ninety-three consecutive patients(62 males and 31 females) with chronic HCV infection, who had never received antiviral therapy or recombinant EPO, were enrolled in the study. Circulating anti-EPO were detected in the serum by using an ELISA assay. Quantitative determination of serum EPO levels was done by radioimmunoassay. HCV RNA viral load measurement and genotype sequencing were also performed.RESULTS: Circulating anti-EPO were detected in 10.8% of HCV-infected patients and the prevalence of anti-EPO was significantly higher in patients with anemia(19.4% vs 5.3%, P=0.040) compared to that in those without anemia. Compared to anti-EPO negative cases, anti-EPO positive patients had higher frequency of anemia(70.0% vs 34.9%, P=0.030), lower EPO concentrations(median 16.35 vs 30.65 m U/m L, P=0.005), and higher HCV RNA viral load(median 891.5×103 vs 367.5×103 IU/m L, P=0.016). In multivariate regression analysis the presence of anti-EPO remained an independent predictor of anemia(adjusted OR: 14.303, 95% CI: 1.417-36.580, P=0.024). EPO response to anemia was less prominent among anti-EPO positive patients(P=0.001).CONCLUSIONS: Circulating anti-EPO are detected in a significant proportion of treatment-na?ve HCV-infected patients and are independently associated with anemia, suggesting a further implication of autoimmunity in the pathophysiology of HCV-related anemia.
文摘AIM: To investigate the presence of autoantibodies directed against liver sinusoidal cells in primary biliary cirrhosis(PBC).METHODS: Liver biopsies from 21 PBC patients were studied and compared with 12 liver biopsies from disease controls [3 patients with hepatitis B(HBV) virus,3 patients with hepatitis C virus(HCV), 3 patients with non-alcoholic steatohepatitis and 3 patients with acute alcoholic hepatitis(AAH)]. As healthy controls, we used tissue specimens adjacent to metastatic liver adenocarcinoma. Normal serum was taken from staff members of the unit. The determination of the cell type targetedby autoantibodies present in the patients sera was performed by indirect immunofluorescence(IIF) analysis using paraffin-embedded liver sections as a substrate.Sera from homologous or heterologous PBC patients or sera from the disease control group were used as primary antibodies. The presence of autoantibodies was identified using confocal microscopy.RESULTS: In total, 18/21(85.7%) PBC patients exhibited positive staining in the sinusoidal cells, 10/21(47.6%) in lymphocytes, 8/21(38%) in cholangiocytes and 7/21(33.3%) in hepatocytes, when homologous serum and fluorescein isothiocyanate-conjugated immunoglobulin type G(IgG) secondary antibody were used. PBC sections incubated with heterologous PBC serum showed reduced staining(20% for sinusoidal cells, 20% for lymphocytes, 20% for cholangiocytes and 13.3% for hepatocytes). When IgM immunoglobulin, instead of IgG, was used as secondary antibody,positive staining was observed in 75% of lymphocytes,62.5% of cholangiocytes, 37.5% of hepatocytes and50% of the sinusoidal cells with a much stronger staining intensity. No staining was observed when either normal or PBC sera were used as a primary antibody on liver sections from the disease control group. When PBC sera were incubated with healthy control sections,weak positive staining of cholangiocytes was observed in 3/21(14.3%) PBC serum samples. Steatohepatitis serum on PBC sections gave a positive staining of some hepatocytes and lymphocytes but no staining on viral hepatitis sections. Incubation with HBV sera stained some hepatocytes, cholangiocytes and intra-sinusoidal or portal lymphocytes of PBC, HBV and AAH patients but not HCV patients.CONCLUSION: In this study, for the first time in diseased liver tissue, we have demonstrated that a large proportion of PBC patients have disease specific autoantibodies against liver sinusoidal cells.
基金the Beijing Natural Science Foundation (No. 7174306)。
文摘Objective To determine the possible association of anti-β1-adrenergic receptors(anti-β1-AR), anti-β2-AR and anti-α1-AR with carvedilol treatment in patients with heart failure(HF). Methods A total of 267 HF patients were prospectively enrolled. Blood samples were measured by an enzyme-linked immunosorbent assay. All of the patients received carvedilol for their HF. Each patient was followed up for six months and their cardiac function was measured. Results The final analysis encompassed 137 patients comprising 65 patients with three autoantibodies(positive group) and 72 patients without all three autoantibodies but with one or two autoantibodies(negative group). The frequency and geometric mean titer of anti-β1-AR, anti-β2-AR, and anti-α1-AR were significantly lower in the group without all three autoantibodies after six months of carvedilol treatment(all P < 0.01;from 100% to 57%, 50%, and 49%, respectively;and from 1: 118, 1: 138, and 1: 130 to 1: 72, 1: 61, and 1: 67, respectively). Furthermore, 28 patients in the positive group demonstrated complete ablation of autoantibodies. In addition, left ventricular remodelling and function was significantly improved by the use of carvedilol combined with the standard treatment regime for six months in the positive group(P < 0.01) when compared to the negative group(P < 0.05). Conclusions Carvedilol treatment significantly decreases frequency and geometric mean titer in patients with all three autoantibodies, even up to complete ablation, and significantly improved cardiac function and remodelling. The effect of carvedilol is probably correlated to the presence of all three autoantibodies.
文摘We have previously reported the high levels of glutamic acid decarboxylase 65 autoantibodies(GAD65A)in patients with type 1 diabetes and autoimmune thyroid disease.Here we describe a 32-year-old Japanese female with a thirteen-year history of type 1 diabetes whose levels of GAD65A were elevated just after the emergence of anti-thyroid autoimmunity.At 19 years of age,she developed diabetic ketoacidosis and was diagnosed with type 1 diabetes.She had GAD65A,insulinoma-associated antigen-2 autoantibodies(IA-2A),and zinc transporter-8 autoantibodies(ZnT8A),but was negative for antibodies to thyroid peroxidase(TPOAb)and thyroglobulin(TGAb)at disease onset.ZnT8A and IA-2A turned negative 2-3 years after the onset,whereas GAD65A were persistently positive at lower level(approximately 40 U/mL).However,just after the emergence of TGAb at disease duration of 12.5 years,GAD65A levels were reelevated up to5717 U/mL in the absence of ZnT8A and IA-2A.Her thyroid function was normal and TPOAb were consistently negative.She has a HLA-DRB1*03:01/*04:01-DQB1*02:01/*03:02 genotype.Persistent positivity for GAD65A might be associated with increased risk to develop anti-thyroid autoimmunity.
基金This study was supported by the National Natural Science Fundation of China (No. 30080027,39570673).
文摘OBJECTIVE: To develope a new enzyme immune assay (ELISA) for detection of M2 antibody specificfor primary biliary cirrhosis (PBC) by using a triple hybrid clone as antigen, which coexpresses the threeimmunodominant lipoyl domains of PDC-E2, BCOADC-E2 and OGDC-E2 from human sources.METHODS: After expressing autoantigens of PBC in prokaryote by constructing recombinant expressiveplasmid successfully, the fusion protein was purified by affinity chromatography. The sera of 17 PBCpatients were examined. As controls, the sera of 167 non-PBC patients and the sera of 1225 normalcontrols aged under 28 were examined.RESULTS: None of the sera from the non-PBC patients or the normal controls was positive for anti-M2shown by the new ELISA. However, the positivity rate for anti-M2 in the PBC patients was 100%(17/17), as shown by the new ELISA.CONCLUSION: The detection system with a good sensitivity and specificity may be used as a powerfulmethod for the diagnosis of PBC.
基金This work was supported by the financial support of the PI17CIII/00045 and PI20CIII/00019 grants from the AES-ISCIII program to R.B.The financial support of the PID2019-103899RB-I00(Ministerio de Ciencia e Innovación)Research Project and the TRANSNANOAVANSENS-CM Program from the Comunidad de Madrid(S2018/NMT-4349)to S.C.are gratefully acknowledged.+3 种基金G.D.acknowledges the financial support of PI15/00246 grant of the FIS and Cátedra UAM-Roche en Medicina de InnovaciónThe FPU predoctoral contract to A.M.-C.is supported by the Spanish Ministerio de Educación,Cultura y Deporte.G.S.-F.is recipient of a predoctoral contract(1193818 N)supported by The Flanders Research Foundation(FWO).M.A.-N.was supported by a contract of the Programa Operativo de Empleo Juvenily la Iniciativa de Empleo Juvenil(YEI)with the participation of the Consejería de Educación,Juventud y Deporte de la Comunidad de Madrid y del Fondo Social EuropeoThe predoctoral contract from the Spanish Ministerio de Economía y Competitividad(BES-2016-076606,E.P.)Talento-Contract from Comunidad de Madrid(2019-T2/IND-15965,R.M.T.-R.)are also gratefully acknowledged.
文摘Colorectal cancer(CRC)is the second leading cause of cancer-related death worldwide.The five-year survival rate of CRC patients depends on the stage at diagnosis,being higher than 80%when CRC is diagnosed in the early stages but lower than 10%when CRC is diagnosed in advanced stages.Autoantibodies against specific CRC autoantigens(tumor-associated antigens(TAAs))in the sera of patients have been widely demonstrated to aid in early diagnosis.Thus,we herein aim to identify autoantigens target of autoantibodies specific to CRC that possess a significant ability to discriminate between CRC patients and healthy individuals by means of liquid biopsy.To that end,we examined the protein content of the exosomes released by five CRC cell lines and tissue samples from CRC patients by means of immunoprecipitation coupled with mass spectrometry analysis.A total of 103 proteins were identified as potential autoantigens specific to CRC.After bioinformatics and meta-analysis,we selected 15 proteins that are more likely to be actual CRC autoantigens in order to evaluate their role in CRC prognosis by Western blot(WB)and immunohistochemistry(IHC).We found dysregulation at the protein level for 11 of these proteins in both tissue and plasma exosome samples from patients,along with an association of nine of these proteins with CRC prognosis.After validation,all but one showed a statistically significant high diagnostic ability to distinguish CRC patients and individuals with premalignant lesions from healthy individuals,either by luminescence Halotag-based beads,or by a multiplexed biosensing platform involving the use of magnetic microcarriers as solid support modified with covalently immobilized Halotag fusion proteins constructed for CRC detection.Taken together,our results highlight the usefulness of the approach defined here to identify the TAAs specific to chronic diseases;they also demonstrate that the measurement of autoantibody levels in plasma against the TAAs identified here could be integrated into a point-of-care(POC)device for CRC detection with high diagnostic ability.
文摘Aim: To determine the clinical and immunological characteristics of patients with systemic erythematosus lupus in Abidjan. Patients and Method: We studied 117 patients’ files with systemic lupus erythematosus aged 12 to 73 years old, who fulfilled the American College of Rheumatology (ACR)’s criteria. Antinuclear autoantibodies (ANA) were searched by indirect immunofluorescence. Anti-DNA native autoantibodies, extractable nuclear anti-antigens autoantibodies (anti-Sm, anti-SSA, anti-SSB and anti-RNP) and anti-phospholipids autoantibodies have been searched by ELISA technic. Results: The most frequent clinical manifestations were: articular damages (86.32%), cutaneous and mucosal lesions (71.79%) and fever (76.67%). Kidney damages have been noticed in 40.17%. Neurologic manifestations have been observed in 36.75%. Pericarditis and pleurisies have been noticed in 22.22% and 11.97% of cases, and anaemia in 86.32% of cases. ANA have been detected in 94.12% of cases, anti-DNA native’s autoantibodies in 73.53% and anti-Sm autoantibodies in 75% of cases. Anti-SSA and anti-SSB autoantibodies were respectively in 75% and 56.25% of cases. Anti-RNP autoantibodies were in all the patients, and anti-phospholipids autoantibodies were in 37.50% of cases. Conclusion: Systemic lupus erythematosus of Ivorian black subject is characterised by high prevalence of autoantibodies, mostly Anti-RNP.
文摘We have studied the level of autoantibodies to neurospecific proteins and neurotransmitters in patients with different forms of ischemic brain lesion. 49 patients with acute (ishemic stroke) and chronic cerebrovascular disease, 14 patients with ishemic heart disease and control group (35 healthy subjects) were investigated. The serum level of autoantibodies to glial fibrillary acidic protein (GFAP) and to dopamine (D) was determinated by ELISA. The content of autoantibodies to GFAP and D in patients with ischemic heart disease was practically identical. The patients with acute and chronic cerebrovas-cular diseases had the significally increased level of autoantibodies. The level of autoantibodies to GFAP in patients with acute vascular accidents (ischemic stroke) with favorable outcome was significantly higher than in patients with chronic cerebral ischemia. The obtained data allowed us to consider serum level of autoantibodies to GFAP as a marker of ischemic brain lesion, and to suppose further potential role of this autoantibodies in cerebrovascular disease progression.
文摘Background: Low-dose computed tomography (CT) screening reduces lung cancer mortality but costs are prohibitive for most healthcare budgets due to high false positive rates. An adjunctive test able to distinguish malignant from benign pulmonary nodules would be hugely beneficial. EarlyCDT-Lung measures serum autoantibodies to tumor-associated antigens and has found clinical acceptance to aid early detection of lung cancer for high risk patients. However performance was optimized for screening. The construction of a receiver-operating characteristic (ROC) curve would enable optimization of performance for alternative settings, including nodule malignancy. Methods: A Monte-Carlo search method was used to construct a ROC curve using a case-control cohort, enabling high and low specificity versions of EarlyCDT-Lung to be determined. These were used for a theoretical evaluation of a nodule cohort, and positive predictive value (PPV) was calculated under the assumption of independence of risk source. Patients or their nodules are typically classified into three risk groups: low (0% - 10%), intermediate (10% - 65%) and high (>65%) risk of malignancy. The predicted shift in risk group by application of the high and low specificity versions, along with the current commercial EarlyCDT-Lung, was then estimated. Results: The ROC curve, with an area under the curve of 0.743, was constructed. The high specificity (98%), low specificity (49%) and current commercial (91% specificity) versions of EarlyCDT-Lung re-classified 27%, 23% and 26% of intermediate nodules, respectively, to either a higher (10%, 8% and 10%) or lower (17%, 15% and 16%) risk group. Conclusion: A ROC curve was constructed to allow performance prediction of EarlyCDT-Lung at different specificities in the indeterminate nodule setting. This enabled risk re-classification of intermediate risk nodules, and could therefore facilitate alternative more appropriate intervention. We have shown how a multivariate biomarker test can add to the interpretation of pulmonary nodules and therefore aid patient management.
文摘Background: We wanted to determine (via an immunopharmacological approach) whether the c-Jun NH2 terminal kinase (JNK) cascade is phosphorylated in the submandibular gland by carbachol and cholinergic autoantibodies (IgG) present in the sera of patients with primary Sj?gren’s syndrome (pSS) by interaction and activation of salivary gland muscarinic acetylcholine receptors (mAChRs). Methods: The JNK, PGE2 and NOS assays were measured in rat sub- mandibular gland with pSS IgG and carbachol alone or in the presence of different blocker agents. Results: pSS IgG- activated M3 mAChRs stimulated JNK phosphorylation whereas the activation of M1 mAChRs by carbachol stimulated JNK phosphorylation involving calcium-activated mechanism. The intracellular pathway leading to pSS IgG-induced biological effects on JNK activity involved activation of protein kinase C (PKC), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) enzymes. Also, activation of COX-2 and COX-1 by pSS IgG and carbachol-induced PGE2 generation were involved. Conclusion: These results may contribute to better understanding the modulatory role of JNK enzymes by cholinergic autoantibodies from pSS patients acting on mAChR in rat submandibular gland.
文摘Background: Type 1 Diabetes mellitus (T1DM) results from a cellular-mediated autoimmune destruction of the β-cells of the pancreas. We designed this study to determine the prevalence of autoantibodies among Saudis patients with T1DM. Methods: Glutamic acid decarboxylase antibodies (GADA), antibodies to Islet cell (ICA) and Insulin (IAA) were measured in 171 Saudis patients with T1DM. Results: There were 171 patients with T1DM, 71 males (41.5%) and 100 females (58.5%). The mean age was 20.8 ± 6.6 and the mean diabetes duration was 7.7 ± 5.7. GADA, ICA and IAA were detected in 53.8%, 32.2% and 76% respectively. GADA, ICA and IAA were nonsignificantly more frequent in female and GADA and IAA were significantly more frequent in those younger than 20 years of age. Subjects testing positive for GADA had higher levels of ICA (42.4% vs. 20.3, p = 0.003) and IAA (79.3% vs. 72.2, p = 0.3) than those negative for GADA. Multiple antibodies (≥2) were observed more often in patients under the age of 20 years. There were nonsignificant differences in the prevalence of multiple antibodies between both genders. Multiple logistic regression analysis showed a significant independent positive relationship between the serum positivity of GADA, ICA and Multiple antibodies (≥2) with diabetes duration (0.02, p = 0.03, 0.02, p = 0.01 and 0.01, p = 0.04 respectively). Conclusions: The prevalence of autoantibodies in Saudi patients with T1DM is similar to those reported for diabetic patients in other ethnic groups.
