To investigate the serum substantia nigra neuron autoantibody and its effect in the patients with Parkinson disease (PD), substantia nigra slices and a rat model of injection of serum from PD patients in unilateral si...To investigate the serum substantia nigra neuron autoantibody and its effect in the patients with Parkinson disease (PD), substantia nigra slices and a rat model of injection of serum from PD patients in unilateral side substantia nigra were applied. The results showed that the positive rate of substantia nigra neuron autoantibody in PD patients was significantly higher than in the healthy control group (36.67 % vs 6.67 %, P <0.01), but no significant difference was found between PD group and myasthenia gravis (MG) group (26.67 %, P >0.05). The sera from PD patients positive for substantia nigra neuron autoantibody could decrease the number of the dopaminergic neurons more seriously than those from MG and the healthy once respectively (both P <0.01). The results suggested that the immunological mechanism might partly play a role in the development of PD.展开更多
Objective: To study the clinical significance of anti-ENA autoantibody profiles and its relationship withother immune markers. Methods: AntiuENA autoantibodies were tested with Western--blot while immunoglobulinsand c...Objective: To study the clinical significance of anti-ENA autoantibody profiles and its relationship withother immune markers. Methods: AntiuENA autoantibodies were tested with Western--blot while immunoglobulinsand complements were detected quantitatively by turbidimetry. Results: 1. High positive rate of anti--ENAautoantibody was detected but not specific in several autoimmune diseases; 2. lgG and IgA was increased in antiENA antibody positive sera while IgM, C3 and C4 was decreased; 3. Elevation of IgG and decrease of IgM, C3and CHS, were correlated with the number of bands of anti-- ENA autoantibodies by immunoblot; 4. Associationbetween clinical activity of diseases and C3, C4 and CH50 were tested. Conclusion: Humoral immune activation wasdemonstrated in patients with positive ENA autoantibody and positively correlated with the number of bands ofanti-- ENA autoantibodies.展开更多
On the basis of the detection of IgG anti-keratin autoantibody (AK auto Ab)in human body fluids,it was shown that IgG AK auto Ab could hardly pass the blood-brain barrier,but it could easily penetrate the capillary wa...On the basis of the detection of IgG anti-keratin autoantibody (AK auto Ab)in human body fluids,it was shown that IgG AK auto Ab could hardly pass the blood-brain barrier,but it could easily penetrate the capillary walls into epithelial tissues.Un-der electron microscope,the interaction between AK auto Ab and keratinocyte is largelylocated in tonofilaments and desmosomes and is irrelevant to other organellae.Dynamicobservations of AK auto Ab suggest that the accumulation of AK auto Ab in keratinocy-te cytoplasm and transitory decrease of IgG AK auto Ab in serum of rabbits with sodiumsulfide dermatitis are related predominantly to keratinocytic injury.展开更多
Background: Detection of autoantibodies has played a consolidate role in diagnosis of systemic autoimmune disorders. A cascade autoantibody testing is usually performed by employing antinuclear antibodies (ANA) test a...Background: Detection of autoantibodies has played a consolidate role in diagnosis of systemic autoimmune disorders. A cascade autoantibody testing is usually performed by employing antinuclear antibodies (ANA) test as a first screening test and the other tests as second level determinations. Here, we present that supplementing extractable nuclear antigens (ENA) tests to the ANA test may capture more autoimmunity and provide critical medical information at an early stage. In this study, we?evaluated the clinical significance of a multiplex ANA + ENA panel. Methods: A cohort of 110 subjects, identified as ANA negative but ENA positive, were followed up for two years. The detection of their ANA and anti-ENA autoantibodies was assessed with a multiplex ANA + ENA panel at Vibrant America Clinical Laboratory. Results: During two years of multi-visit follow-up, 23 out of 110 subjects (20.9%) were found to become ANA positive within an average of 385 (±144) days. Histone (50/110, 45.5%) and Chromatin (25/110, 22.7%) antibodies were the most frequently found antibodies at their first visits. The subjects who were positive for RNP (5/8, 62.5%) and SSA (Ro) (10/22, 45.5%) have the highest ratio of conversion to positive ANA. No significant correlation was observed between the conversion frequency and the number of anti-ENA antibodies being carried. Conclusion: This study, which followed up on the subjects who had disparate ANA and ENA test results, showed that anti-ENA antibodies may exist years earlier than ANA. Combining ENA tests with ANA screening may reduce false negatives and improve sensitivity.展开更多
Autoimmune haemolytic anaemia is a haemolytic disease resulting from an autoimmune reaction to the surface of red blood cells. A part of autoantibody is known to react with the blood type antigen. This is the case of ...Autoimmune haemolytic anaemia is a haemolytic disease resulting from an autoimmune reaction to the surface of red blood cells. A part of autoantibody is known to react with the blood type antigen. This is the case of a 14 years old female with Evans syndrome in which autoimmune haemolysis may cause from anti-Jka autoantibody reaction. As this case is complicated with primary IgA immunodeficiency syndrome, anti-Jka autoantibody may occur under the condition of primary immunodeficiency status, in which autoantibody production is accelerated. Considering the co-occurrence of autoimmune haemolytic anaemia and primary IgA immunodeficiency syndrome, analysis focusing on specificity for red blood cells antigens will be required in IgA immunodefi-ciency syndrome patients.展开更多
Objectives Autoantibodies play a key role in mechanism of rheumatic heart disease(RHD) and in this research,we focus on identifying the autoantibody in Chinese RHD patients which can be a potential molecular biomarker...Objectives Autoantibodies play a key role in mechanism of rheumatic heart disease(RHD) and in this research,we focus on identifying the autoantibody in Chinese RHD patients which can be a potential molecular biomarker. Methods To construct RHD expression library,the total RNA of heart tissue of RHD patients was extracted and mRNA was isolated,purified and reverse-transcripted to long cDNA.Phage was used to recombining cDNA to be expression library.The library was immunoscreened by serum of active rheumatic fever patients,An autoantigen positive clone was immunoscreened.To identify the autoantibody,autoantibody gene was analysed by PCR,sequencing and bioinfor-matics. It also was subcloned and expressed in vitro.Western blotting was used to identify the expression protein and test cross-reaction effect with serum.Results An expression library with heart tissue of RHD patients was successfully established. The titer of the primary library was 3.3×10~6 pfu/ml, recombinant rate of it was 99%and 81%inserted segments were larger than 1 kb.A positive antoantibody gene was sreened and it is homologous to keratin 18.The recombined vector could expression objective protein in vitro which could be reacted with sera of active rheumatic fever patients and rheumatic heart disease patients,but could not be detected by sera of health persons.Conclusions It is an effective strategy to investigate autoantigens of Chinese RHD that constructing and immunoscreening heart tissues expression library. This research implied that keratin 18 was a candidate molecular biomarker of RHD.展开更多
Autism spectrum disorder(ASD)is a serious neurodevelopmental disorder,the etiology and mechanism of which are not yet clear.Studies have shown that folate deficiency can lead to abnormalities in the de-velopment of th...Autism spectrum disorder(ASD)is a serious neurodevelopmental disorder,the etiology and mechanism of which are not yet clear.Studies have shown that folate deficiency can lead to abnormalities in the de-velopment of the central nervous system.Patients with autism spectrum disorders develop folate-alpha recep-tor autoantibodies.Folate-alpha receptor autoantibodies block folate transport,leading to a deficiency of folate in nerve tissues.Folate is effective in treating patients with folate-alpha receptor autoantibodies.展开更多
Chronic inflammation associated with hepatitis C virus(HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effe...Chronic inflammation associated with hepatitis C virus(HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effective and less toxic therapeutic options, in most parts of the world the standard treatment consists of a weekly injection of pegylated interferon α(IFN-α) together with a daily dose of ribavirin. HCV patients frequently present circulating non-organ-specific autoantibodies demonstrating a variety of staining patterns in the indirect immunofluorescence assay for antinuclear antibodies(ANA). Between 20% to 40% of HCV patients treated with IFN-α and ribavirin develop autoantibodies showing a peculiar ANA pattern characterized as rods and rings(RR) structures. The aim of this article is to review the recent reports regarding RR structures and anti-rods/rings(antiRR) autoantibody production by HCV patients after IFN-α/ribavirin treatment. Anti-RR autoantibodies first appear around the sixth month of treatment and reach a plateau around the twelfth month. After treatment completion, anti-RR titers decrease/disappear in half the patients and remain steady in the other half. Some studies have observed a higher frequency of anti-RR antibodies in relapsers, i.e., patients in which circulating virus reappears after initially successful therapy. The main target of anti-RR autoantibodies in HCV patients is inosine-5'-monophosphate dehydrogenase 2(IMPDH2), the rate-limiting enzyme involved in the guanosine triphosphate biosynthesis pathway. Ribavirin is a direct IMPDH2 inhibitor and is able to induce the formation of RR structures in vitro and in vivo. In conclusion, these observations led to the hypothesis that anti-RR autoantibody production is a human model of immunologic tolerance breakdown that allows us to explore the humoral autoimmune response from the beginning of the putative triggering event: exposure to ribavirin and interferon.展开更多
Current diagnostic assays for many cancers are antigen-based and rely on the detection of circulating proteins that are associated with a particular cancer.These assays depend on the expression,synthesis,and release o...Current diagnostic assays for many cancers are antigen-based and rely on the detection of circulating proteins that are associated with a particular cancer.These assays depend on the expression,synthesis,and release of specific proteins by cells(e.g.,tumor cells)through either active secretion or shedding,or as a consequence of cell death(either necrosis or apoptosis).As such,these antigenic proteins must“escape”the primary site of disease,saturate the antigen-processing capacity of the individual’s immune components,gain access to the circulation,and reach a sufficient steady-state concentration to be detected by enzyme-or radiolabel-based immunoassays.These events usually occur after the initial establishment of disease.Thus,and despite the fact that certain specific antigenic epitopes exhibit common recognition among patients with the same tumor types,the use of these antigen-based cancer assays has not been widely accepted in clinical practice,and many individual countries differ in the use of these potential diagnostic factors.Lately,an increasing number of studies demonstrated that procathepsin D secreted from cancer cells,acts as a mitogen on cancer cells and stimulates their pro-invasive and pro-metastatic properties.In this report,we focused on the possibility to use antiprocathepsin D autoantibodies as a diagnostic and/or predictive marker for cancers.展开更多
AIM To determine how the auto-antibodies(Abs) profiles overlap in chronic hepatitis C infection(CHC) and autoimmune hepatitis(AIH) and correlate to liver disease.METHODS Levels of antinuclear Ab, smooth muscle antibod...AIM To determine how the auto-antibodies(Abs) profiles overlap in chronic hepatitis C infection(CHC) and autoimmune hepatitis(AIH) and correlate to liver disease.METHODS Levels of antinuclear Ab, smooth muscle antibody(SMA) and liver/kidney microsomal-1(LKM-1) Ab and markers of liver damage were determined in the sera of 50 patients with CHC infection, 20 AIH patients and 20 healthy controls using enzyme linked immunosorbent assay and other immune assays. RESULTS We found that AIH patients had more severe liver disease as determined by elevation of total Ig G, alkaline phosphatase, total serum bilirubin and serum transaminases and significantly higher prevalence of the three non-organ-specific autoantibodies(auto-Abs) than CHC patients. Antinuclear Ab, SMA and LKM-1 Ab were also present in 36% of CHC patients and related to disease severity. CHC cases positive for auto-Abs were directly comparable to AIH in respect of most markers of liver damage and total Ig G. These cases had longer disease duration compared with auto-Ab negative cases, but there was no difference in gender, age or viral load. KLM-1+ Ab CHC cases showed best overlap with AIH. CONCLUSION Auto-Ab levels in CHC may be important markers of disease severity and positive cases have a disease similar to AIH. Auto-Abs might have a pathogenic role as indicated by elevated markers of liver damage. Future studies will unravel any novel associations between these two diseases, whether genetic or other.展开更多
BACKGROUND Autoimmune antibodies are detected in many diseases.Viral infections are accompanied by several immunopathological manifestations.Some autoimmune antibodies have been associated with the immune response ind...BACKGROUND Autoimmune antibodies are detected in many diseases.Viral infections are accompanied by several immunopathological manifestations.Some autoimmune antibodies have been associated with the immune response induced by virus or drugs.Thus,a comprehensive diagnosis of chronic hepatitis B combined with autoimmune hepatitis is required,and immunosuppressant or antiviral therapy should be carefully considered.CASE SUMMARY We present a case of a patient who had negative transformation of autoimmune antibodies during chronic active hepatitis B.A 50-year-old female who had a history of asymptomatic hepatitis B virus carriers for more than 10 years presented to the hospital with the complaint of weakness for 1 wk.Blood tests revealed elevated liver enzymes;the detection of autoantibodies was positive.Hepatitis B viral load was 72100000 IU/mL.The patient started tenofovir alafenamide fumigate 25 mg daily.Liver biopsy was performed,which was consistent with chronic active hepatitis B.The final diagnosis of the case was chronic active hepatitis B.The autoimmune antibodies turned negative after 4 wk of antiviral therapy.The patient recovered and was discharged with normal liver function.There was no appearance of autoantibodies,and liver function was normal at regular follow-ups.CONCLUSION Autoimmune antibodies may appear in patients with chronic active hepatitis.It is necessary to differentiate the diagnosis with autoimmune hepatitis.展开更多
Background: Current screening mammography for breast cancer is associated with misdiagnosis in as many as 30% of cases. Objectives: To develop and clinically evaluate a unique autoantibody based protein microarray blo...Background: Current screening mammography for breast cancer is associated with misdiagnosis in as many as 30% of cases. Objectives: To develop and clinically evaluate a unique autoantibody based protein microarray blood test to improve the accuracy of breast cancer screening. Materials and Methods: A microarray was constructed from commercial antigens and antigens selected from screened cDNA libraries of breast cancer tissue samples. A training set containing 439 healthy controls and 276 biopsy proven breast cancer cases was used to establish a set of separating models between the two groups. These models were used to assign a diagnosis to 285 blind samples from 120 breast cancer patients and 165 healthy controls. Results: The test identified 82 of the 120 breast cancer patients and 160 of the 165 healthy controls. These results can be translated into a sensitivity of 68.3% [CI: 59% -77%] and a specificity of 97% [CI: 93% -99%], with a PPV for this validation set of 94.3% (CI: 87.10% -98.11%), NPV of 80.81% [CI: 74.62% -86.05%] and an AUC of 89.2% [CI: 78% -87%]. Conclusions: The protein microarray can be utilized to reduce the false negative rate of routine screening mammography. Women with a negative mammography and a negative blood test can be reassured and encouraged to continue routine breast cancer screening. A positive test should alert the physician about the possible presence of a breast cancer not detected by routine screening mammography and drive to perform additional investigation, such as breast ultrasound and MRI.展开更多
Objective: To purify the natural antikeratin autoantibody (AK auto-Ab) and observe its effects on the prolif eration of the cultured keratinocytes. Methods: Natural AK auto-Ab was purified by using keratin affinity co...Objective: To purify the natural antikeratin autoantibody (AK auto-Ab) and observe its effects on the prolif eration of the cultured keratinocytes. Methods: Natural AK auto-Ab was purified by using keratin affinity column, and then the titre and specificity of the Abs were studied by ELISA, immunoperoxidase staining and immuno-electronicmicroscope. The effect of the purified Abs on the cultured keratino-cytes was assayed by 3H-TdR incorporation. Results: Natural AK auto-Ab was obtained. The binding activity of IgG AK auto-Ab in purified Ah remained similar to that in pooled human sera. and the specificity of the obtained antibody is strong. The purified antibody could decrease the Il-TdR incorporation of the cultured keratinocytes in a dose-dependent manner. Conclusion: The method of punning AK auto-Ab is simple, practicable and reliable. Natural AK auto-Ab, existing in normal human individuals, has inhibitory etiect on the proliferation of the cultured keratinocytes.展开更多
BACKGROUND In recent years,the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediat...BACKGROUND In recent years,the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediated type 1 diabetes(T1D).While it has been established that 20%-30%of T1D patients suffer from autoimmune thyroid disease(AITD),there is limited available data regarding the presence of anti-islet autoantibodies in AITD patients.Among commercially available anti-islet autoantibodies,glutamic acid decarboxylase 65 autoantibodies(GADAs)are often the first marker measured in general clinical practice.AIM To investigate the frequency of anti-islet autoantibodies in AITD patients.METHODS Our study involved four hundred ninety-five AITD patients,categorized into three distinct groups:AITD with T1D(n=18),AITD with phenotypic type 2 diabetes(T2D)(n=81),and AITD without diabetes(n=396),and the enzyme-linked immunosorbent assay(ELISA)was employed to determine the frequencies of 3 Screen Islet Cell Autoantibody(3 Screen ICA),GADA,insulinoma-associated antigen-2 autoantibodies(IA-2As),and zinc transporter 8 autoantibodies(ZnT8As)within these groups.RESULTS The frequency of 3 Screen ICA in AITD patients with T1D,T2D,and those without diabetes were 88.9%,6.2%,and 5.1%,respectively,with no significant difference seen between the latter two groups.Notably,the frequency of 3 Screen ICA was 11.1%higher in AITD patients with T1D,1.3%higher in AITD patients with T2D,and 1.1%higher in AITD patients without diabetes compared to GADA,respectively.Furthermore,12.5%,20.0%,and 20.0%of the 3 Screen ICA-positive patients were negative for GADA.Additionally,1.3%of the AITD patients who tested negative for 3 Screen ICA in both the AITD with T2D and non-diabetic AITD groups were found to be positive for individual autoantibodies.Among the 3 Screen ICA-positive patients,there was a significantly higher proportion of individuals with multiple autoantibodies in AITD patients with T1D compared to those without diabetes(37.5%vs 5.0%,P<0.05).However,this proportion was similar to that in AITD patients with T2D(20.0%).Nevertheless,there was no significant difference in 3 Screen ICA titers between AITD patients with T1D and those without diabetes(436.8±66.4 vs 308.1±66.4 index).Additionally,no significant difference in 3 Screen ICA titers was observed between Graves’disease and Hashimoto’s thyroiditis in any of the groups.CONCLUSION Our findings reveal that some AITD patients without diabetes exhibit 3 Screen ICA titers comparable to those in AITD patients with T1D.Thus,3 Screen ICA outperforms GADA in identifying latent anti-islet autoantibody-positive individuals among AITD patients.展开更多
Autoantibody(AAb)detection has become one of the standards of diagnosis for autoimmune liver disease(AILD),and some AAbs have become specific biomarkers of AILD.In addition,AAbs can be detected in patients with non-AI...Autoantibody(AAb)detection has become one of the standards of diagnosis for autoimmune liver disease(AILD),and some AAbs have become specific biomarkers of AILD.In addition,AAbs can be detected in patients with non-AILDs,such as viral hepatitis and alcoholic liver disease.However,the distribution characteristics and pathogenic mechanisms of AAbs in patients with non-AILD are unclear.This article summarizes the characteristics of AAbs in several common clinical chronic liver diseases(CLDs)and discusses the value of AAb analysis in CLD.展开更多
Neuromyelitis optica is an inflammatory demyelinating disease of the central nervous system that differs from multiple sclerosis.Over the past 20 years,the search for biomarke rs for neuromyelitis optica has been ongo...Neuromyelitis optica is an inflammatory demyelinating disease of the central nervous system that differs from multiple sclerosis.Over the past 20 years,the search for biomarke rs for neuromyelitis optica has been ongoing.Here,we used a bibliometric approach to analyze the main research focus in the field of biomarkers for neuromyelitis optica.Research in this area is consistently increasing,with China and the United States leading the way on the number of studies conducted.The Mayo Clinic is a highly reputable institution in the United States,and was identified as the most authoritative institution in this field.Furthermore,Professor Wingerchuk from the Mayo Clinic was the most authoritative expe rt in this field.Keyword analysis revealed that the terms "neuro myelitis optica"(261 times), "multiple sclerosis"(220 times), "neuromyelitis optica spectrum disorder"(132 times), "aquaporin4"(99 times),and "optical neuritis"(87 times) were the most frequently used keywords in literature related to this field.Comprehensive analysis of the classical literature showed that the majority of publications provide conclusive research evidence supporting the use of aquaporin-4-IgG and neuromyelitis optica-IgG to effectively diagnose and differentiate neuromyelitis optica from multiple sclerosis.Furthermore,aquaporin-4-IgG has emerged as a highly specific diagnostic biomarker for neuromyelitis optica spectrum disorder.Myelin oligodendrocyte glycoprotein-IgG is a diagnostic biomarke r for myelin oligodendrocyte glycoprotein antibody-associated disease.Recent biomarkers for neuromyelitis optica in clude cerebrospinal fluid immunological biomarkers such as glial fibrillary acidic protein,serum astrocyte damage biomarkers like FAM19A5,serum albumin,and gammaaminobutyric acid.The latest prospective clinical trials are exploring the potential of these biomarkers.Preliminary results indicate that glial fibrillary acidic protein is emerging as a promising candidate biomarker for neuromyelitis optica spectrum disorder.The ultimate goal of future research is to identify non-invasive biomarkers with high sensitivity,specificity,and safety for the accurate diagnosis of neuro myelitis optica.展开更多
Autoimmune pancreatitis(AIP)is a rare chronic autoimmune disorder.The diagnosis of AIP mainly depends on histopathology,imaging and response to treatment.Serum immunoglobulin 4(IgG4)is used only as collateral evidence...Autoimmune pancreatitis(AIP)is a rare chronic autoimmune disorder.The diagnosis of AIP mainly depends on histopathology,imaging and response to treatment.Serum immunoglobulin 4(IgG4)is used only as collateral evidence in diagnostic criteria for AIP because of its moderate sensitivity.Serum IgG4 levels are normal in 15%-37%of type 1 AIP and most of type 2 AIP patients.In these patients,the indeterminate imaging and histopathology may lead to the difficulty in definitive diagnosis of AIP.Therefore,discovery of new biomarkers is impor-tant for AIP diagnosis.Here,we provide some views on the progression and challenges in identifying novel serological biomarkers in AIP diagnosis.展开更多
目的:探讨血清基质金属蛋白酶-1(matrix metalloproteinase-1,MMP1)和纽约食管鳞状细胞癌抗原-1(New York esophageal squamous cell carcinoma 1,NY-ESO-1)自身抗体联合检测在食管鳞状细胞癌中的诊断意义。方法:应用酶联免疫吸附实验检...目的:探讨血清基质金属蛋白酶-1(matrix metalloproteinase-1,MMP1)和纽约食管鳞状细胞癌抗原-1(New York esophageal squamous cell carcinoma 1,NY-ESO-1)自身抗体联合检测在食管鳞状细胞癌中的诊断意义。方法:应用酶联免疫吸附实验检测120例食管鳞状细胞癌患者和120例正常对照血清中MMP1和NY-ESO-1自身抗体的表达水平,采用受试者工作特征(receiver operating characteristic,ROC)曲线评价诊断效能。结果:血清MMP1和NY-ESO-1自身抗体在食管鳞状细胞癌患者中的表达均明显高于正常对照[(8.070±5.738)ng/mL vs(4.331±3.137)ng/mL,Z=6.214,P<0.001;0.463±0.571 vs 0.156±0.086,Z=5.210,P<0.001]。ROC曲线显示,当血清MMP1为最佳诊断临界值10.586 ng/mL时,其在诊断食管鳞状细胞癌的曲线下面积(area under the ROC curve,AUC)为0.732(95%CI:0.671~0.787),敏感度为24.2%,特异度为95.0%。NY-ESO-1自身抗体诊断食管鳞状细胞癌AUC为0.695(95%CI:0.632~0.752),敏感度为33.0%,特异度为95.0%。MMP1和NY-ESO-1自身抗体联合检测诊断食管鳞状细胞癌的AUC为0.800(95%CI:0.744~0.849),敏感度为47.5%,特异度为95.0%。结论:血清MMP1和NY-ESO-1自身抗体联合检测可能有助于提高食管鳞状细胞癌的诊断效能。展开更多
Immunodeficiency due to anti-interferon-gamma（anti-IFN-γ） autoantibody is an emerging adult-onsetimmunodeficiency syndrome associated with severeor disseminated infections caused by non-tuberculousmycobacteria, non...Immunodeficiency due to anti-interferon-gamma（anti-IFN-γ） autoantibody is an emerging adult-onsetimmunodeficiency syndrome associated with severeor disseminated infections caused by non-tuberculousmycobacteria, non-typhoidal salmonella, Burkholderiasp., Penicillium marneffei, Cryptococcus neoformans,Histoplasma capsulatum, and varicella zoster virus （VZV）in non-HIV-infected patients caused by the presence ofhigh-titer serum neutralizing anti-lFN-~ autoantibodieswhich inhibit IFN-γ-induced STAT1 phosphorylationand interleukin-12 production,1-3 It was first reportedin an otherwise immunocompetent Filipino man withdisseminated Myeobacterium chelonae infection in 2004.1Since then, the condition has been increasingly reported inAsians including Filipino, Thai, Vietnamese, Japanese, andChinese residents from Hong Kong and Taiwan, and lesscommonly in other ethnic groups1。展开更多
文摘To investigate the serum substantia nigra neuron autoantibody and its effect in the patients with Parkinson disease (PD), substantia nigra slices and a rat model of injection of serum from PD patients in unilateral side substantia nigra were applied. The results showed that the positive rate of substantia nigra neuron autoantibody in PD patients was significantly higher than in the healthy control group (36.67 % vs 6.67 %, P <0.01), but no significant difference was found between PD group and myasthenia gravis (MG) group (26.67 %, P >0.05). The sera from PD patients positive for substantia nigra neuron autoantibody could decrease the number of the dopaminergic neurons more seriously than those from MG and the healthy once respectively (both P <0.01). The results suggested that the immunological mechanism might partly play a role in the development of PD.
文摘Objective: To study the clinical significance of anti-ENA autoantibody profiles and its relationship withother immune markers. Methods: AntiuENA autoantibodies were tested with Western--blot while immunoglobulinsand complements were detected quantitatively by turbidimetry. Results: 1. High positive rate of anti--ENAautoantibody was detected but not specific in several autoimmune diseases; 2. lgG and IgA was increased in antiENA antibody positive sera while IgM, C3 and C4 was decreased; 3. Elevation of IgG and decrease of IgM, C3and CHS, were correlated with the number of bands of anti-- ENA autoantibodies by immunoblot; 4. Associationbetween clinical activity of diseases and C3, C4 and CH50 were tested. Conclusion: Humoral immune activation wasdemonstrated in patients with positive ENA autoantibody and positively correlated with the number of bands ofanti-- ENA autoantibodies.
基金The project was supported by National Natural Science Foundation of China
文摘On the basis of the detection of IgG anti-keratin autoantibody (AK auto Ab)in human body fluids,it was shown that IgG AK auto Ab could hardly pass the blood-brain barrier,but it could easily penetrate the capillary walls into epithelial tissues.Un-der electron microscope,the interaction between AK auto Ab and keratinocyte is largelylocated in tonofilaments and desmosomes and is irrelevant to other organellae.Dynamicobservations of AK auto Ab suggest that the accumulation of AK auto Ab in keratinocy-te cytoplasm and transitory decrease of IgG AK auto Ab in serum of rabbits with sodiumsulfide dermatitis are related predominantly to keratinocytic injury.
文摘Background: Detection of autoantibodies has played a consolidate role in diagnosis of systemic autoimmune disorders. A cascade autoantibody testing is usually performed by employing antinuclear antibodies (ANA) test as a first screening test and the other tests as second level determinations. Here, we present that supplementing extractable nuclear antigens (ENA) tests to the ANA test may capture more autoimmunity and provide critical medical information at an early stage. In this study, we?evaluated the clinical significance of a multiplex ANA + ENA panel. Methods: A cohort of 110 subjects, identified as ANA negative but ENA positive, were followed up for two years. The detection of their ANA and anti-ENA autoantibodies was assessed with a multiplex ANA + ENA panel at Vibrant America Clinical Laboratory. Results: During two years of multi-visit follow-up, 23 out of 110 subjects (20.9%) were found to become ANA positive within an average of 385 (±144) days. Histone (50/110, 45.5%) and Chromatin (25/110, 22.7%) antibodies were the most frequently found antibodies at their first visits. The subjects who were positive for RNP (5/8, 62.5%) and SSA (Ro) (10/22, 45.5%) have the highest ratio of conversion to positive ANA. No significant correlation was observed between the conversion frequency and the number of anti-ENA antibodies being carried. Conclusion: This study, which followed up on the subjects who had disparate ANA and ENA test results, showed that anti-ENA antibodies may exist years earlier than ANA. Combining ENA tests with ANA screening may reduce false negatives and improve sensitivity.
文摘Autoimmune haemolytic anaemia is a haemolytic disease resulting from an autoimmune reaction to the surface of red blood cells. A part of autoantibody is known to react with the blood type antigen. This is the case of a 14 years old female with Evans syndrome in which autoimmune haemolysis may cause from anti-Jka autoantibody reaction. As this case is complicated with primary IgA immunodeficiency syndrome, anti-Jka autoantibody may occur under the condition of primary immunodeficiency status, in which autoantibody production is accelerated. Considering the co-occurrence of autoimmune haemolytic anaemia and primary IgA immunodeficiency syndrome, analysis focusing on specificity for red blood cells antigens will be required in IgA immunodefi-ciency syndrome patients.
文摘Objectives Autoantibodies play a key role in mechanism of rheumatic heart disease(RHD) and in this research,we focus on identifying the autoantibody in Chinese RHD patients which can be a potential molecular biomarker. Methods To construct RHD expression library,the total RNA of heart tissue of RHD patients was extracted and mRNA was isolated,purified and reverse-transcripted to long cDNA.Phage was used to recombining cDNA to be expression library.The library was immunoscreened by serum of active rheumatic fever patients,An autoantigen positive clone was immunoscreened.To identify the autoantibody,autoantibody gene was analysed by PCR,sequencing and bioinfor-matics. It also was subcloned and expressed in vitro.Western blotting was used to identify the expression protein and test cross-reaction effect with serum.Results An expression library with heart tissue of RHD patients was successfully established. The titer of the primary library was 3.3×10~6 pfu/ml, recombinant rate of it was 99%and 81%inserted segments were larger than 1 kb.A positive antoantibody gene was sreened and it is homologous to keratin 18.The recombined vector could expression objective protein in vitro which could be reacted with sera of active rheumatic fever patients and rheumatic heart disease patients,but could not be detected by sera of health persons.Conclusions It is an effective strategy to investigate autoantigens of Chinese RHD that constructing and immunoscreening heart tissues expression library. This research implied that keratin 18 was a candidate molecular biomarker of RHD.
基金Yunnan Provincial Department of Education Scien-tific Research Fund Project(K13225116).
文摘Autism spectrum disorder(ASD)is a serious neurodevelopmental disorder,the etiology and mechanism of which are not yet clear.Studies have shown that folate deficiency can lead to abnormalities in the de-velopment of the central nervous system.Patients with autism spectrum disorders develop folate-alpha recep-tor autoantibodies.Folate-alpha receptor autoantibodies block folate transport,leading to a deficiency of folate in nerve tissues.Folate is effective in treating patients with folate-alpha receptor autoantibodies.
基金Supported by Brazilian government research foundations National Council for Research and Technology and Coordination for the Improvement of Higher Education Personnel with research grant and scholarships processNo.9028-11-0+2 种基金No.305064/2011-8 and No.232711/2014-3Sao Paulo Government agency Sao Paulo State Research Foundation withprocess No.2011/12448-0both granted to Andrade LEC and Keppeke GD
文摘Chronic inflammation associated with hepatitis C virus(HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effective and less toxic therapeutic options, in most parts of the world the standard treatment consists of a weekly injection of pegylated interferon α(IFN-α) together with a daily dose of ribavirin. HCV patients frequently present circulating non-organ-specific autoantibodies demonstrating a variety of staining patterns in the indirect immunofluorescence assay for antinuclear antibodies(ANA). Between 20% to 40% of HCV patients treated with IFN-α and ribavirin develop autoantibodies showing a peculiar ANA pattern characterized as rods and rings(RR) structures. The aim of this article is to review the recent reports regarding RR structures and anti-rods/rings(antiRR) autoantibody production by HCV patients after IFN-α/ribavirin treatment. Anti-RR autoantibodies first appear around the sixth month of treatment and reach a plateau around the twelfth month. After treatment completion, anti-RR titers decrease/disappear in half the patients and remain steady in the other half. Some studies have observed a higher frequency of anti-RR antibodies in relapsers, i.e., patients in which circulating virus reappears after initially successful therapy. The main target of anti-RR autoantibodies in HCV patients is inosine-5'-monophosphate dehydrogenase 2(IMPDH2), the rate-limiting enzyme involved in the guanosine triphosphate biosynthesis pathway. Ribavirin is a direct IMPDH2 inhibitor and is able to induce the formation of RR structures in vitro and in vivo. In conclusion, these observations led to the hypothesis that anti-RR autoantibody production is a human model of immunologic tolerance breakdown that allows us to explore the humoral autoimmune response from the beginning of the putative triggering event: exposure to ribavirin and interferon.
文摘Current diagnostic assays for many cancers are antigen-based and rely on the detection of circulating proteins that are associated with a particular cancer.These assays depend on the expression,synthesis,and release of specific proteins by cells(e.g.,tumor cells)through either active secretion or shedding,or as a consequence of cell death(either necrosis or apoptosis).As such,these antigenic proteins must“escape”the primary site of disease,saturate the antigen-processing capacity of the individual’s immune components,gain access to the circulation,and reach a sufficient steady-state concentration to be detected by enzyme-or radiolabel-based immunoassays.These events usually occur after the initial establishment of disease.Thus,and despite the fact that certain specific antigenic epitopes exhibit common recognition among patients with the same tumor types,the use of these antigen-based cancer assays has not been widely accepted in clinical practice,and many individual countries differ in the use of these potential diagnostic factors.Lately,an increasing number of studies demonstrated that procathepsin D secreted from cancer cells,acts as a mitogen on cancer cells and stimulates their pro-invasive and pro-metastatic properties.In this report,we focused on the possibility to use antiprocathepsin D autoantibodies as a diagnostic and/or predictive marker for cancers.
文摘AIM To determine how the auto-antibodies(Abs) profiles overlap in chronic hepatitis C infection(CHC) and autoimmune hepatitis(AIH) and correlate to liver disease.METHODS Levels of antinuclear Ab, smooth muscle antibody(SMA) and liver/kidney microsomal-1(LKM-1) Ab and markers of liver damage were determined in the sera of 50 patients with CHC infection, 20 AIH patients and 20 healthy controls using enzyme linked immunosorbent assay and other immune assays. RESULTS We found that AIH patients had more severe liver disease as determined by elevation of total Ig G, alkaline phosphatase, total serum bilirubin and serum transaminases and significantly higher prevalence of the three non-organ-specific autoantibodies(auto-Abs) than CHC patients. Antinuclear Ab, SMA and LKM-1 Ab were also present in 36% of CHC patients and related to disease severity. CHC cases positive for auto-Abs were directly comparable to AIH in respect of most markers of liver damage and total Ig G. These cases had longer disease duration compared with auto-Ab negative cases, but there was no difference in gender, age or viral load. KLM-1+ Ab CHC cases showed best overlap with AIH. CONCLUSION Auto-Ab levels in CHC may be important markers of disease severity and positive cases have a disease similar to AIH. Auto-Abs might have a pathogenic role as indicated by elevated markers of liver damage. Future studies will unravel any novel associations between these two diseases, whether genetic or other.
文摘BACKGROUND Autoimmune antibodies are detected in many diseases.Viral infections are accompanied by several immunopathological manifestations.Some autoimmune antibodies have been associated with the immune response induced by virus or drugs.Thus,a comprehensive diagnosis of chronic hepatitis B combined with autoimmune hepatitis is required,and immunosuppressant or antiviral therapy should be carefully considered.CASE SUMMARY We present a case of a patient who had negative transformation of autoimmune antibodies during chronic active hepatitis B.A 50-year-old female who had a history of asymptomatic hepatitis B virus carriers for more than 10 years presented to the hospital with the complaint of weakness for 1 wk.Blood tests revealed elevated liver enzymes;the detection of autoantibodies was positive.Hepatitis B viral load was 72100000 IU/mL.The patient started tenofovir alafenamide fumigate 25 mg daily.Liver biopsy was performed,which was consistent with chronic active hepatitis B.The final diagnosis of the case was chronic active hepatitis B.The autoimmune antibodies turned negative after 4 wk of antiviral therapy.The patient recovered and was discharged with normal liver function.There was no appearance of autoantibodies,and liver function was normal at regular follow-ups.CONCLUSION Autoimmune antibodies may appear in patients with chronic active hepatitis.It is necessary to differentiate the diagnosis with autoimmune hepatitis.
文摘Background: Current screening mammography for breast cancer is associated with misdiagnosis in as many as 30% of cases. Objectives: To develop and clinically evaluate a unique autoantibody based protein microarray blood test to improve the accuracy of breast cancer screening. Materials and Methods: A microarray was constructed from commercial antigens and antigens selected from screened cDNA libraries of breast cancer tissue samples. A training set containing 439 healthy controls and 276 biopsy proven breast cancer cases was used to establish a set of separating models between the two groups. These models were used to assign a diagnosis to 285 blind samples from 120 breast cancer patients and 165 healthy controls. Results: The test identified 82 of the 120 breast cancer patients and 160 of the 165 healthy controls. These results can be translated into a sensitivity of 68.3% [CI: 59% -77%] and a specificity of 97% [CI: 93% -99%], with a PPV for this validation set of 94.3% (CI: 87.10% -98.11%), NPV of 80.81% [CI: 74.62% -86.05%] and an AUC of 89.2% [CI: 78% -87%]. Conclusions: The protein microarray can be utilized to reduce the false negative rate of routine screening mammography. Women with a negative mammography and a negative blood test can be reassured and encouraged to continue routine breast cancer screening. A positive test should alert the physician about the possible presence of a breast cancer not detected by routine screening mammography and drive to perform additional investigation, such as breast ultrasound and MRI.
文摘Objective: To purify the natural antikeratin autoantibody (AK auto-Ab) and observe its effects on the prolif eration of the cultured keratinocytes. Methods: Natural AK auto-Ab was purified by using keratin affinity column, and then the titre and specificity of the Abs were studied by ELISA, immunoperoxidase staining and immuno-electronicmicroscope. The effect of the purified Abs on the cultured keratino-cytes was assayed by 3H-TdR incorporation. Results: Natural AK auto-Ab was obtained. The binding activity of IgG AK auto-Ab in purified Ah remained similar to that in pooled human sera. and the specificity of the obtained antibody is strong. The purified antibody could decrease the Il-TdR incorporation of the cultured keratinocytes in a dose-dependent manner. Conclusion: The method of punning AK auto-Ab is simple, practicable and reliable. Natural AK auto-Ab, existing in normal human individuals, has inhibitory etiect on the proliferation of the cultured keratinocytes.
文摘BACKGROUND In recent years,the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediated type 1 diabetes(T1D).While it has been established that 20%-30%of T1D patients suffer from autoimmune thyroid disease(AITD),there is limited available data regarding the presence of anti-islet autoantibodies in AITD patients.Among commercially available anti-islet autoantibodies,glutamic acid decarboxylase 65 autoantibodies(GADAs)are often the first marker measured in general clinical practice.AIM To investigate the frequency of anti-islet autoantibodies in AITD patients.METHODS Our study involved four hundred ninety-five AITD patients,categorized into three distinct groups:AITD with T1D(n=18),AITD with phenotypic type 2 diabetes(T2D)(n=81),and AITD without diabetes(n=396),and the enzyme-linked immunosorbent assay(ELISA)was employed to determine the frequencies of 3 Screen Islet Cell Autoantibody(3 Screen ICA),GADA,insulinoma-associated antigen-2 autoantibodies(IA-2As),and zinc transporter 8 autoantibodies(ZnT8As)within these groups.RESULTS The frequency of 3 Screen ICA in AITD patients with T1D,T2D,and those without diabetes were 88.9%,6.2%,and 5.1%,respectively,with no significant difference seen between the latter two groups.Notably,the frequency of 3 Screen ICA was 11.1%higher in AITD patients with T1D,1.3%higher in AITD patients with T2D,and 1.1%higher in AITD patients without diabetes compared to GADA,respectively.Furthermore,12.5%,20.0%,and 20.0%of the 3 Screen ICA-positive patients were negative for GADA.Additionally,1.3%of the AITD patients who tested negative for 3 Screen ICA in both the AITD with T2D and non-diabetic AITD groups were found to be positive for individual autoantibodies.Among the 3 Screen ICA-positive patients,there was a significantly higher proportion of individuals with multiple autoantibodies in AITD patients with T1D compared to those without diabetes(37.5%vs 5.0%,P<0.05).However,this proportion was similar to that in AITD patients with T2D(20.0%).Nevertheless,there was no significant difference in 3 Screen ICA titers between AITD patients with T1D and those without diabetes(436.8±66.4 vs 308.1±66.4 index).Additionally,no significant difference in 3 Screen ICA titers was observed between Graves’disease and Hashimoto’s thyroiditis in any of the groups.CONCLUSION Our findings reveal that some AITD patients without diabetes exhibit 3 Screen ICA titers comparable to those in AITD patients with T1D.Thus,3 Screen ICA outperforms GADA in identifying latent anti-islet autoantibody-positive individuals among AITD patients.
基金Talent Development Plan for Beijing High-level Public Health Technical Personnel Project,Grant/Award Number:2022-2-014。
文摘Autoantibody(AAb)detection has become one of the standards of diagnosis for autoimmune liver disease(AILD),and some AAbs have become specific biomarkers of AILD.In addition,AAbs can be detected in patients with non-AILDs,such as viral hepatitis and alcoholic liver disease.However,the distribution characteristics and pathogenic mechanisms of AAbs in patients with non-AILD are unclear.This article summarizes the characteristics of AAbs in several common clinical chronic liver diseases(CLDs)and discusses the value of AAb analysis in CLD.
文摘Neuromyelitis optica is an inflammatory demyelinating disease of the central nervous system that differs from multiple sclerosis.Over the past 20 years,the search for biomarke rs for neuromyelitis optica has been ongoing.Here,we used a bibliometric approach to analyze the main research focus in the field of biomarkers for neuromyelitis optica.Research in this area is consistently increasing,with China and the United States leading the way on the number of studies conducted.The Mayo Clinic is a highly reputable institution in the United States,and was identified as the most authoritative institution in this field.Furthermore,Professor Wingerchuk from the Mayo Clinic was the most authoritative expe rt in this field.Keyword analysis revealed that the terms "neuro myelitis optica"(261 times), "multiple sclerosis"(220 times), "neuromyelitis optica spectrum disorder"(132 times), "aquaporin4"(99 times),and "optical neuritis"(87 times) were the most frequently used keywords in literature related to this field.Comprehensive analysis of the classical literature showed that the majority of publications provide conclusive research evidence supporting the use of aquaporin-4-IgG and neuromyelitis optica-IgG to effectively diagnose and differentiate neuromyelitis optica from multiple sclerosis.Furthermore,aquaporin-4-IgG has emerged as a highly specific diagnostic biomarker for neuromyelitis optica spectrum disorder.Myelin oligodendrocyte glycoprotein-IgG is a diagnostic biomarke r for myelin oligodendrocyte glycoprotein antibody-associated disease.Recent biomarkers for neuromyelitis optica in clude cerebrospinal fluid immunological biomarkers such as glial fibrillary acidic protein,serum astrocyte damage biomarkers like FAM19A5,serum albumin,and gammaaminobutyric acid.The latest prospective clinical trials are exploring the potential of these biomarkers.Preliminary results indicate that glial fibrillary acidic protein is emerging as a promising candidate biomarker for neuromyelitis optica spectrum disorder.The ultimate goal of future research is to identify non-invasive biomarkers with high sensitivity,specificity,and safety for the accurate diagnosis of neuro myelitis optica.
文摘Autoimmune pancreatitis(AIP)is a rare chronic autoimmune disorder.The diagnosis of AIP mainly depends on histopathology,imaging and response to treatment.Serum immunoglobulin 4(IgG4)is used only as collateral evidence in diagnostic criteria for AIP because of its moderate sensitivity.Serum IgG4 levels are normal in 15%-37%of type 1 AIP and most of type 2 AIP patients.In these patients,the indeterminate imaging and histopathology may lead to the difficulty in definitive diagnosis of AIP.Therefore,discovery of new biomarkers is impor-tant for AIP diagnosis.Here,we provide some views on the progression and challenges in identifying novel serological biomarkers in AIP diagnosis.
文摘目的:探讨血清基质金属蛋白酶-1(matrix metalloproteinase-1,MMP1)和纽约食管鳞状细胞癌抗原-1(New York esophageal squamous cell carcinoma 1,NY-ESO-1)自身抗体联合检测在食管鳞状细胞癌中的诊断意义。方法:应用酶联免疫吸附实验检测120例食管鳞状细胞癌患者和120例正常对照血清中MMP1和NY-ESO-1自身抗体的表达水平,采用受试者工作特征(receiver operating characteristic,ROC)曲线评价诊断效能。结果:血清MMP1和NY-ESO-1自身抗体在食管鳞状细胞癌患者中的表达均明显高于正常对照[(8.070±5.738)ng/mL vs(4.331±3.137)ng/mL,Z=6.214,P<0.001;0.463±0.571 vs 0.156±0.086,Z=5.210,P<0.001]。ROC曲线显示,当血清MMP1为最佳诊断临界值10.586 ng/mL时,其在诊断食管鳞状细胞癌的曲线下面积(area under the ROC curve,AUC)为0.732(95%CI:0.671~0.787),敏感度为24.2%,特异度为95.0%。NY-ESO-1自身抗体诊断食管鳞状细胞癌AUC为0.695(95%CI:0.632~0.752),敏感度为33.0%,特异度为95.0%。MMP1和NY-ESO-1自身抗体联合检测诊断食管鳞状细胞癌的AUC为0.800(95%CI:0.744~0.849),敏感度为47.5%,特异度为95.0%。结论:血清MMP1和NY-ESO-1自身抗体联合检测可能有助于提高食管鳞状细胞癌的诊断效能。
文摘Immunodeficiency due to anti-interferon-gamma（anti-IFN-γ） autoantibody is an emerging adult-onsetimmunodeficiency syndrome associated with severeor disseminated infections caused by non-tuberculousmycobacteria, non-typhoidal salmonella, Burkholderiasp., Penicillium marneffei, Cryptococcus neoformans,Histoplasma capsulatum, and varicella zoster virus （VZV）in non-HIV-infected patients caused by the presence ofhigh-titer serum neutralizing anti-lFN-~ autoantibodieswhich inhibit IFN-γ-induced STAT1 phosphorylationand interleukin-12 production,1-3 It was first reportedin an otherwise immunocompetent Filipino man withdisseminated Myeobacterium chelonae infection in 2004.1Since then, the condition has been increasingly reported inAsians including Filipino, Thai, Vietnamese, Japanese, andChinese residents from Hong Kong and Taiwan, and lesscommonly in other ethnic groups1。
