Introduction: Prostate cancer is the second most common cancer in men. The diagnosis is most often based on the prostate biopsies’ analysis and on histological criteria recognizable on standard coloring. In some case...Introduction: Prostate cancer is the second most common cancer in men. The diagnosis is most often based on the prostate biopsies’ analysis and on histological criteria recognizable on standard coloring. In some cases, the use of immunohistochemistry is important. Objectives: This paper aims to specify the p63 phenotypic profile of lesions diagnosed benign, with minimal suspect foci, difficult to interpret, HGPIN (high grade intraepithelial neoplasia) and LGPIN (low-grade prostatic intraepithelial neoplasia) and evaluate the manual technique of p63 immunohistochemistry. Patients and Method: This was a retrospective, descriptive study of prostate biopsies recorded in the PAC service of the HALD from January 1st, 2018 to December 31st, 2018. It was completed by a manual immunohistochemical study of the blocks enrolled from November 19th to December 4th, 2020 in the PAC department of the HPD. The studied parameters were: registry number, age, clinical stage, prostate volume, PSA level, microscopic appearance and p63 immunohistochemical profile. Results: Our study included 60 prostate biopsies. The ages of our patients varied from 45 to 77 years, with an average of 64.2 years and a standard deviation of 6.2. The majority of patients were at clinical stage cT2b (33%) with a prostate volume varying between 33.15 and 169.4 cc. The minimum value of PSA in our series is 5 ng/ml, the maximum being 100 ng/ml with an average level of 24.1 ng/ml and a standard deviation of 21.2. Our series included 50 adenomyomatous hyperplasias, 7 adenomyomatous hyperplasias associated with chronic prostatitis, 2 HGPIN and 1 LGPIN. After re-reading we found 5 discordant cases, which corresponded to minimal suspect foci (kappa = 0.5098). The p63 marking was informative in 53 cases, i.e. 88%, and non-informative in 7 cases, i.e. 12%. Among the uninformative markings, 2 were due to lack of tissue adhesion to the slides. Among the informative markings, 11 were negative. p63 immunohistochemistry was useful in all suspected foci and detected 6 other minimal foci of adenocarcinoma. Conclusion: The immunostaining with the anti-p63 antibody in the prostate cancer diagnosis is of considerable benefit. It made it possible to correct 11.3% of benign diagnosis in minimal malignant focus in our context. Despite the difficulties associated with the manual technique, it is possible to have an informative rate, similar to the automatic technique.展开更多
This observational prospective study was conducted on 25 patients who had received a full 3-dose COVID-19 vaccination scheme with a follow-up ranging from 12 to 19 months after the last injection. The aim of the study...This observational prospective study was conducted on 25 patients who had received a full 3-dose COVID-19 vaccination scheme with a follow-up ranging from 12 to 19 months after the last injection. The aim of the study was focused on a single biological indicator the anti-spike IgG antibody titer. The age of the patients ranged from 51 to 85 years old. 15 out 25 patients (60%) presented a comorbidity. Our data showed a persistent positive anti-spike IgG antibodies titer ranging from 105 to 5680 BAU/mL (mean: 2661 BAU/mL) in all patients. In view of these results, systematic administration of a SARS-CoV-2 vaccine booster is questionable and should be individually tailored according to the patient medical condition and the anti-spike IgG antibody level.展开更多
Anti β NGF antiserum was prepared by immunizing rabbits with purified mouse β NGF. It presented immunopositivity to β NGF on Western blot, resulting in a single band approximately at the molecular weight of 14 kD...Anti β NGF antiserum was prepared by immunizing rabbits with purified mouse β NGF. It presented immunopositivity to β NGF on Western blot, resulting in a single band approximately at the molecular weight of 14 kDa. The antiserum was further purified into anti β NGF IgG by affinity chromatography. Chicken embryonic dorsal root ganglia (DRG) were cultured to test the biological activities of β NGF and its antibody.展开更多
Primary biliary cirrhosis(PBC) is a chronic,progressive,cholestatic,organ-specific autoimmune disease of unknown etiology.It predominantly affects middle-aged women,and is characterized by autoimmune-mediated destruct...Primary biliary cirrhosis(PBC) is a chronic,progressive,cholestatic,organ-specific autoimmune disease of unknown etiology.It predominantly affects middle-aged women,and is characterized by autoimmune-mediated destruction of small-and medium-size intrahepatic bile ducts,portal inflammation and progressive scarring,which without proper treatment can ultimately lead to fibrosis and hepatic failure.Serum autoantibodies are crucial tools for differential diagnosis of PBC.While it is currently accepted that antimitochondrial antibodies are the most important serological markers of PBC,during the last five decades more than sixty autoantibodies have been explored in these patients,some of which had previously been thought to be specific for other autoimmune diseases.展开更多
AIM:To investigate possible associations of anti-nuclear envelope antibody(ANEA)with disease severity and survival in Greek primary biliary cirrhosis(PBC)patients.METHODS:Serum samples were collected at diagnosis from...AIM:To investigate possible associations of anti-nuclear envelope antibody(ANEA)with disease severity and survival in Greek primary biliary cirrhosis(PBC)patients.METHODS:Serum samples were collected at diagnosis from 147 PBC patients(85%female),who were followed-up for a median 89.5 mo(range 1-240).ANEA were detected with indirect immunofluorescence on 1% formaldehyde fixed Hep2 cells,and anti-gp210 antibodies were detected using an enzyme linked immunosorbent assay.Findings were correlated with clinical data,histology,and survival.RESULTS:ANEA were detected in 69/147(46.9%) patients and 31/147(21%)were also anti-gp210 positive.The ANEA positive patients were at a more advanced histological stage(Ⅰ-Ⅱ/Ⅲ-Ⅳ56.5%/43.5% vs 74.4%/25.6%,P=0.005)compared to the ANEA negative ones.They had a higher antimitochondrial antibodies(AMA)titer(≤1:160/>1:160 50.7%/49.3%vs 71.8%/28.2%,P=0.001)and a lower survival time(91.7 ±50.7 mo vs 101.8±55 mo,P=0.043).Moreover,they had more advanced fibrosis,portal inflammation,interface hepatitis,and proliferation of bile ductules(P =0.008,P=0.008,P=0.019,and P=0.027,respectively).They also died more frequently of hepatic failure and/or hepatocellular carcinoma(P=0.016).ANEA positive,anti-gp210 positive patients had a difference in stage(Ⅰ-Ⅱ/Ⅲ-Ⅳ54.8%/45.2%vs 74.4%/25.6%,P= 0.006),AMA titer(≤1:160/>1:160 51.6%/48.4%vs 71.8%/28.2%,P=0.009),survival(91.1±52.9 mo vs 101.8±55 mo,P=0.009),and Mayo risk score(5.5 ±1.9 vs 5.04±1.3,P=0.04)compared to the ANEA negative patients.ANEA positive,anti-gp210 negative patients had a difference in AMA titer(≤1:160/>1:160 50%/50%vs 71.8%/28.2%,P=0.002),stage(Ⅰ-Ⅱ/Ⅲ -Ⅳ57.9%/42.1%vs 74.4%/25.6%,P=0.033),fibrosis(P=0.009),portal inflammation(P=0.018),interface hepatitis(P=0.032),and proliferation of bile ductules(P=0.031).Anti-gp210 positive patients had a worse Mayo risk score(5.5±1.9 vs 4.9±1.7,P=0.038)than the anti-gp210 negative ones.CONCLUSION:The presence of ANEA and anti-gp210 identifies a subgroup of PBC patients with advanced disease severity and poor prognosis.展开更多
AIM To analyze the clinical impact of preformed antiH LA-Cw vs antiH LA-A and/or-B donor-specific antibodies(DSA) in kidney transplantation.METHODS Retrospective study, comparing 12 patients transplanted with DSA excl...AIM To analyze the clinical impact of preformed antiH LA-Cw vs antiH LA-A and/or-B donor-specific antibodies(DSA) in kidney transplantation.METHODS Retrospective study, comparing 12 patients transplanted with DSA exclusively antiH LA-Cw with 23 patients with preformed DSA antiH LA-A and/or B.RESULTS One year after transplantation there were no differencesin terms of acute rejection between the two groups(3 and 6 cases, respectively in the DSA-Cw and the DSA-A-B groups; P = 1). At one year, eG FR was not significantly different between groups(median 59 mL /min in DSA-Cw group, compared to median 51 mL /min in DSA-A-B group, P = 0.192). Moreover, kidney graft survival was similar between groups at 5-years(100% in DSA-Cw group vs 91% in DSA-A-B group, P = 0.528). The sole independent predictor of antibody mediated rejection(AMR) incidence was DSA strength(HR = 1.07 per 1000 increase in MFI, P = 0.034). AMR was associated with shortened graft survival at 5-years, with 75% and 100% grafts surviving in patients with or without AMR, respectively(Log-rank P = 0.005).CONCLUSION Our data indicate that DSA-Cw are associated with an identical risk of AMR and impact on graft function in comparison with "classical" class I DSA.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
AIM: To identify the role of anti-pancreatic antibody (PAB) in the diagnosis of inflammatory bowel diseases (IBD) among Turkish patients, and its frequency in firstdegree relatives.METHODS: PAB and anti-Saccharomyces ...AIM: To identify the role of anti-pancreatic antibody (PAB) in the diagnosis of inflammatory bowel diseases (IBD) among Turkish patients, and its frequency in firstdegree relatives.METHODS: PAB and anti-Saccharomyces cerevisiae (ASCA) were examined in serum samples of 214 subjects including patients with Crohn's disease (CD, n = 64), ulcerative colitis (UC, n = 63), first-degree relatives of patients with CD (n = 25), first-degree relatives of patients with UC (n = 28),and a control group with gastrointestinal symptoms other than (IBD) (n = 34) by indirect immunofluorescence Positivity of PAB and ASCA was compared in terms of Vienna classification, disease activity and medications used.RESULTS: In terms of PAB positivity, no difference was found between patients with CD (14.1%) and UC (7.9%) however, significant difference was observed between patients with CD and subjects in the control group (P < 0.05). No difference was found between patients with CD and their relatives in terms of ASCA positivity, whereas a significant difference was found between other groups (P < 0.001). Compared to ASCA, the sensitivity of the PAB was 19% (7/37), its specificity was 93% (25/27), positive predictive value was 77% (7/9) and negative predictive value was 45% (25/55). ASCA was found with significantly higher prevalence in patients with CD activity index > 150 (P < 0.05).CONCLUSION: PAB is valuable in the diagnosis of IBD rather than CD, but cannot be used alone for diagnostic purposes. PAB is not superior to ASCA in CD diagnosis and in detecting CD among relatives of patients with CD.展开更多
Summary: To study whether there was an anti-cardiac myosin antibody (AMA) in serum of pa- tients with myocardial infarction (AMI), relationship between AMA and the prognosis in patients with AMI was investigated. In 6...Summary: To study whether there was an anti-cardiac myosin antibody (AMA) in serum of pa- tients with myocardial infarction (AMI), relationship between AMA and the prognosis in patients with AMI was investigated. In 67 patients with acute AMI, AMA was assayed by ELISA and left ventricular structure and cardiac function were examined by echocardiography at the end of the first week after infarction and during a 6-month follow-up. The patients with AMI were divided into AMA-positive group and AMA-negative group. The parameters of left ventricular end-dias- tolic function and prognosis were compared between the two groups. Results showed that the AMA was positive in 18 patients with AMI, with a positive rate of 26. 87 %, while it was negative in 20 health donors. The locations of myocardial infarction in the two groups were similar. There were significant differences in Killip class I (22. 22 % vs 55. 10 %, P<0. 05), decreasing of wall motion and ventricular aneurysm (92. 85 % vs 37. 5 %, P<0.01) between the positive group and the negative group. During a 6-month follow-up, the mortality was higher in AMA positive group than in AMA negative group (38. 89% vs 10. 20 %, P<0. 05). It is concluded that AMA can be detected in serum of patients with AMI and can serve as an important autoimmune marker. The autoimmune response might take place in AMI. AMA was associated with the left ventricular re- modeling and the prognosis of AMI.展开更多
Mutation of the p53 gene is a key event in the carcinogenesis of many different types of tumours. These can occur throughout the length of the p53 gene. Anti-p53 auto-antibodies are commonly produced in response to th...Mutation of the p53 gene is a key event in the carcinogenesis of many different types of tumours. These can occur throughout the length of the p53 gene. Anti-p53 auto-antibodies are commonly produced in response to these p53 mutations. This review firstly describes the various mechanisms of p53 dysfunction and their association with subsequent carcinogenesis. Following this, the mechanisms of induction of anti-p53 auto-antibody production are shown, with various hypotheses for the discrepancies between the presence of p53 mutation and the presence/absence of anti-p53 auto-antibodies. A systematic review was performed with a descriptive summary of key findings of each anti-p53 auto-antibody study in all cancers published in the last 30 years. Using this, the cumulative frequency of anti-p53 autoantibody in each cancer type is calculated and then compared with the incidence of p53 mutation in each cancer to provide the largest sample calculation and correlation between mutation and anti-p53 auto-antibody published to date. Finally, the review focuses onthe data of anti-p53 auto-antibody in colorectal cancer studies, and discusses future strategies including the potentially promising role using anti-p53 auto-antibody presence in screening and surveillance.展开更多
AIM To investigate near-infrared photoimmunotherapeutic effect mediated by an anti-tissue factor(TF) antibody conjugated to indocyanine green(ICG) in a pancreatic cancer model.METHODS Near-infrared photoimmunotherapy(...AIM To investigate near-infrared photoimmunotherapeutic effect mediated by an anti-tissue factor(TF) antibody conjugated to indocyanine green(ICG) in a pancreatic cancer model.METHODS Near-infrared photoimmunotherapy(NIR-PIT) is a highly selective tumor treatment that utilizes an antibody-photosensitizer conjugate administration, followed by NIR light exposure. Anti-TF antibody 1849-ICG conjugate was synthesized by labeling of rat IgG2 b anti-TF monoclonal antibody 1849(anti-TF 1849) to a NIR photosensitizer,ICG. The expression levels of TF in two human pancreatic cancer cell lines were examined by western blotting. Specific binding of the 1849-ICG to TF-expressing BxPC-3 cells was examined by fluorescence microscopy. NIR-PITinduced cell death was determined by cell viability imaging assay. In vivo longitudinal fluorescence imaging was used to explore the accumulation of 1849-ICG conjugate in xenograft tumors. To examine the effect of NIRPIT, tumor-bearing mice were separated into 5 groups:(1) 100 μg of 1849-ICG i.v. administration followed by NIR light exposure(50 J/cm2) on two consecutive days(Days 1 and 2);(2) NIR light exposure(50 J/cm2) only on two consecutive days(Days 1 and 2);(3) 100 μg of 1849-ICG i.v. administration;(4) 100 μg of unlabeled antiTF 1849 i.v. administration; and(5) the untreated control. Semiweekly tumor volume measurements, accompanied with histological and immunohistochemical(IHC) analyses of tumors, were performed 3 d after the 2nd irradiation with NIR light to monitor the effect of treatments. RESULTS High TF expression in BxPC-3 cells was observed via western blot analysis, concordant with the observed preferential binding with intracellular localization of 1849-ICG via fluorescence microscopy. NIR-PIT-induced cell death was observed by performing cell viability imaging assay. In contrast to the other test groups, tumor growth was significantly inhibited by NIR-PIT with a statistically significant difference in relative tumor volumes for 27 d after the treatment start date [2.83 ± 0.38(NIR-PIT) vs 5.42 ± 1.61(Untreated), vs 4.90 ± 0.87(NIR), vs 4.28 ±1.87(1849-ICG), vs 4.35 ± 1.42(anti-TF 1849), at Day 27, P < 0.05]. Tumors that received NIR-PIT showed evidence of necrotic cell death-associated features upon hematoxylin-eosin staining accompanied by a decrease in Ki-67-positive cells(a cell proliferation marker) by IHC examination.CONCLUSION The TF-targeted NIR-PIT with the 1849-ICG conjugate can potentially open a new platform for treatment of TF-expressing pancreatic cancer.展开更多
The suppressive effect of anti-KDR antibody against VEGF on proliferation of hemangioma-derived vascular endothelial cells （HVECs） was investigated. HVECs from one case of hemangioma in proliferative phase were cult...The suppressive effect of anti-KDR antibody against VEGF on proliferation of hemangioma-derived vascular endothelial cells （HVECs） was investigated. HVECs from one case of hemangioma in proliferative phase were cultured. Both primary culture and sub-culture were conducted in M199 medium. The HVECs of passage 3 were divided into 4 groups based on the concentrations of anti-KDR antibody. Cell count was performed and inhibitory rate of HVECs was measured before and 9 days after interference. The results showed that the number of HVECs in the anti-KDR anti- body-treated groups was significantly decreased and the inhibitory rate of HVECs by anti-KDR antibody （50, 10 and 2 μg/mL） was 84%, 63% and 39% respectively at 9th day after interference, with the difference being significant. In the control group, the number of HVECs was increased significantly. In was concluded that the anti-KDR antibody could suppress the activity of VEGF through blocking the KDR, indicating the potential clinical applications of anti-KDR antibody in the treatment of hemangioma.展开更多
AIM: To assess the prevalence and stability of different antiphospholipid antibodies(APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases(IBD) patients.METHODS: About 458 ...AIM: To assess the prevalence and stability of different antiphospholipid antibodies(APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases(IBD) patients.METHODS: About 458 consecutive patients [Crohn's disease(CD): 271 and ulcerative colitis(UC): 187] were enrolled into a follow-up cohort study in a tertiary IBD referral center in Hungary. Detailed clinical phenotypes were determined at enrollment by reviewing the patients' medical charts. Disease activity, medical treatment and data about evolvement of complications or surgical interventions were determined prospectively during the follow-up. Disease course(development f complicated disease phenotype and need for surgery),occurrence of thrombotic events, actual state of diseaseactivity according to clinical, laboratory and endoscopic scores and accurate treatment regime were recorded during the follow-up,(median, 57.4 and 61.6 mo for CD and UC). Sera of IBD patients and 103 healthy controls(HC) were tested on individual anti-β2-Glycoprotein-I(anti-β2-GPI IgA/M/G), anti-cardiolipin(ACA IgA/M/G)and anti-phosphatidylserine/prothrombin(anti-PS/PT IgA/M/G) antibodies and also anti-Saccharomyces cerevisiae antibodies(ASCA IgA/G) by enzyme-linked immunosorbent assay(ELISA). In a subgroup of CD(n = 198) and UC patients(n = 103), obtaining consecutive samples over various arbitrary timepoints during the disease course, we evaluated the intraindividual stability of the APLA status. Additionally,we provide an overview of studies, performed so far, in which significance of APLAs in IBD were assessed.RESULTS: Patients with CD had significantly higher prevalence of both ACA(23.4%) and anti-PS/PT(20.4%) antibodies than UC(4.8%, p < 0.0001 and10.2%, p = 0.004) and HC(2.9%, p < 0.0001 and15.5%, p = NS). No difference was found for the prevalence of anti-β2-GPI between different groups(7.2%-9.7%). In CD, no association was found between APLA and ASCA status of the patients.Occurrence of anti-β2-GPI, ACA and anti-PS/PT was not different between the group of patients with active vs inactive disease state according to appropriate clinical, laboratory and endoscopic scores in CD as well as in UC patients. All subtypes of anti-β2-GPI and ACA IgM status were found to be very stable over time, in contrast ACA IgG and even more ACA IgA status showed significant intraindividual changes.Changes in antibody status were more remarkable in CD than UC(ACA IgA: 49.9% vs 23.3% and ACA IgG:21.2% vs 5.8%). Interestingly, 59.1% and 30.1% of CD patients who received anti-TNF therapy showed significant negative to positive changes in ACA IgA and IgG antibody status respectively. APLA status was not associated with the clinical phenotype at diagnosis or during follow-up, medical therapy, or thrombotic events and it was not associated with the probability of developing complicated disease phenotype or surgery in a Kaplan-Meier analysis.CONCLUSION: The present study demonstrated enhanced formation of APLAs in CD patients. However,presence of different APLAs were not associated with the clinical phenotype or disease course.展开更多
Dendritic cells(DCs) are professinal antigen-presenting cells with the ability to initiate primary Tcell responses. While it iswell known that inflammatory stimuli induce the functional maturation of immature DCs, whe...Dendritic cells(DCs) are professinal antigen-presenting cells with the ability to initiate primary Tcell responses. While it iswell known that inflammatory stimuli induce the functional maturation of immature DCs, whether adhesion molecule selectins regulate DCmaturation is poorly understood. Using anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb) that blocks the adhesionof P-, E-, and L-selectin, we demonstrate herein that selectins play important role in stimulating functional maturation of immature DCs.Immature DCs are generated from human cord blood CD34+hematopoietic stem/progenitor cells that were cultured in the presence of stemcell factor, Fms-like tyrosine-kinase-3 ligand, granulocyte-macrophage colony stimulating factor, and transform growth factor-β1. Whenstimulated with tumor necrosis factor-alpha(TNF-α), immature DCs differentiated into mature DCs, producing increased levels of costim-ulatory molecules and interleukin (IL)-12 and obtaining the ability to potently activate naive Tcells. Interestingly, in contrast to matureDCs derived from TNF-α-induced immature DC cultures without PsL-EGFmAb, immature DCs treated with PsL-EGFmAb for7 days werecompletely blocked their maturation, as evidenced by decreased expression of costimulatory molecules CD80, CD86, and CD83, inhibi-ted production of IL-12, and inability to activate naive Tcellsin vitro. Thus, blockade of selectins using PsL-EGFmAb will prove to bea valuable tool for the study of the molecuar mechanisms of DC maturation, as well as for the prevention and treatment of DC-mediated au-toimmunity.展开更多
Objective： This study was designed to determine the safety, pharmacokinetics and biologic effects of a humanmouse chimeric anti-CD20 monoclonal antibody （SCT400） in Chinese padents with CD20-positive B-cell non- Ho...Objective： This study was designed to determine the safety, pharmacokinetics and biologic effects of a humanmouse chimeric anti-CD20 monoclonal antibody （SCT400） in Chinese padents with CD20-positive B-cell non- Hodgkin＇s lymphoma （CD20 B-cell NHL）. SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians. Methods： Fifteen patients with CD20＋ B-cell NHL received dose-escalating SCT400 infusions （250 mg/m2： n=3; 375 mg/m2： n=9; 500 mg/m2： n=3） once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacoklnetics and pharmacodynamics analyses. Results： No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 ncutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer （NK） cell count or immunoglobulin levels. No patient developed anti- SCT400 antibodies during the course of the study. SCT400 serum half-life （Tin）, maximum concentration （Cmax and area under the curve （AUC） generally increased between the first and fourth infusions （P〈0.05）. At the 375 mg/m2 dose, the T1/2 was 122.5±46.7 h vs. 197.0,75.0 11, respectively, and the Cmax was 200.6±20.2 pg/mL vs. 339.1±71.0 ng/mL, respectively. From 250 mg/m2 to 500 mg/m2, the Cmax and AUC increased significantly in a dose-dependent manner （P〈0.05）. Patients with a high tumor burden had markedly lower serum SCT400 concenmations compared with those without or with a low tumor burden. Of the 9 assessable patients, 1 achieved complete response and 2 achieved partial responses. Conclusions; SCT400 is well-tolerated and has encouraging preliminary efficacy in Chinese patients with CD20＋ B-cell NHL.展开更多
AIM To assess the seroprevalence of hepatitis B virus(HBV) immunity among previously vaccinated pediatric liver transplant recipients and present a case report of de novo hepatitis B infection after liver transplantat...AIM To assess the seroprevalence of hepatitis B virus(HBV) immunity among previously vaccinated pediatric liver transplant recipients and present a case report of de novo hepatitis B infection after liver transplantation.METHODS This study focused on children with chronic liver diseases who received primary hepatitis B immunization and had a complete dataset of anti-HBs before and after liver transplantation between May 2001 and June 2017. Medical records were retrospectively reviewed for potential factors relating to HBV immunity loss. RESULTS In total, 50 children were recruited. The mean time from liver transplantation to anti-HBs testing was 2.53 ± 2.11 years. The mean anti-HBs levels before and after liver transplantation were 584.41 ± 415.45 and 58.56 ± 6.40 IU/L, respectively. The rate of nonimmunity(anti-HBs < 10 IU/L) in the participants was 46%(n = 26) at one year, 57%(n = 7) at two years and 82%(n = 17) at > three years following liver transplantation. The potential factors relating to HBV immunity loss after liver transplantation were identified as anti-HBs(P = 0.002), serum albumin(P = 0.04), total bilirubin(P = 0.001) and direct bilirubin(P = 0.003) before liver transplantation. A five-year-old boy with biliary cirrhosis received 4 doses of HBV vaccine with an anti-HBs titer of > 1000 IU/L and underwent liver transplantation; his anti-HBc-negative father was the donor. After liver transplantation, the boy had stenosis of the hepatic artery up to the inferior vena cava anastomosis and underwent venoplasty three times. He also received subcutaneous injections of enoxaparin for 5 mo and 20 transfusions of blood components. Three years and ten months after the liver transplantation, transaminitis was detected with positive tests for HBs Ag, HBe Ag, and anti-HBc(2169.61, 1706 and 8.45, respectively; cutoff value: < 1.00) and an HBV viral load of 33212320 IU/mL.CONCLUSION The present study showed that loss of hepatitis B immunity after liver transplantation is unexpectedly common. In our case report, despite high levels of antiHBs prior to transplantation, infection occurred at a time when, unfortunately, the child had lost immunity to hepatitis B after liver transplantation.展开更多
Objective To study the findings of serum antibodies against annexin V, prothrombin, ph-inositol, ph-acid, ph-ethanolamine, ph-serine, ph-glycerol, cardiolipin, and beta2-glycoprotein I and analyze the trophoblast anne...Objective To study the findings of serum antibodies against annexin V, prothrombin, ph-inositol, ph-acid, ph-ethanolamine, ph-serine, ph-glycerol, cardiolipin, and beta2-glycoprotein I and analyze the trophoblast annexin V receptors Methods Sera from 156patients aged 26-41 years with recurrent pregnancy loss （3-7 times） were investigated. Eighty-four fertile healthy women aged 24-38 years were included in a control group. ELISA methods were used for detecting a panel of sera anti-phospholipid antibodies. Immunolocalization of annexin V receptors in 143 trophoblast specimens of 156 patients was investigated by the immunofluorescence technique using Annexin V-FITC, Apoptosis and Annexin V-CY3 commercial kits. Results Positivity for anti-phospholipid antibodies mainly against ph-serine, ph- ethanolamine, and ph-inositol was found together in 80. 8%（126 out of 156 patients）, anti-prothrombin antibodies in 12% （18）, and anti-annexin V antibodies in 13. 5% （21） women. No significant levels of anti-phospholipid antibodies were found in 6 controls. Placenta immunohistopathology also exhibited some changes manifested by the presence of apoptotic and necrotic cells in trophoblast, and very few microthrombotization in some intervillous spaces. Conclusion Our detailed study demonstrated the prevalence of majority of antiphospholipid antibodies as a high risk factor for repeated reproductive failure. Very low microthrombosis in placentas could be explained by the changes of haemocoagulation properties out of uterus.展开更多
文摘Introduction: Prostate cancer is the second most common cancer in men. The diagnosis is most often based on the prostate biopsies’ analysis and on histological criteria recognizable on standard coloring. In some cases, the use of immunohistochemistry is important. Objectives: This paper aims to specify the p63 phenotypic profile of lesions diagnosed benign, with minimal suspect foci, difficult to interpret, HGPIN (high grade intraepithelial neoplasia) and LGPIN (low-grade prostatic intraepithelial neoplasia) and evaluate the manual technique of p63 immunohistochemistry. Patients and Method: This was a retrospective, descriptive study of prostate biopsies recorded in the PAC service of the HALD from January 1st, 2018 to December 31st, 2018. It was completed by a manual immunohistochemical study of the blocks enrolled from November 19th to December 4th, 2020 in the PAC department of the HPD. The studied parameters were: registry number, age, clinical stage, prostate volume, PSA level, microscopic appearance and p63 immunohistochemical profile. Results: Our study included 60 prostate biopsies. The ages of our patients varied from 45 to 77 years, with an average of 64.2 years and a standard deviation of 6.2. The majority of patients were at clinical stage cT2b (33%) with a prostate volume varying between 33.15 and 169.4 cc. The minimum value of PSA in our series is 5 ng/ml, the maximum being 100 ng/ml with an average level of 24.1 ng/ml and a standard deviation of 21.2. Our series included 50 adenomyomatous hyperplasias, 7 adenomyomatous hyperplasias associated with chronic prostatitis, 2 HGPIN and 1 LGPIN. After re-reading we found 5 discordant cases, which corresponded to minimal suspect foci (kappa = 0.5098). The p63 marking was informative in 53 cases, i.e. 88%, and non-informative in 7 cases, i.e. 12%. Among the uninformative markings, 2 were due to lack of tissue adhesion to the slides. Among the informative markings, 11 were negative. p63 immunohistochemistry was useful in all suspected foci and detected 6 other minimal foci of adenocarcinoma. Conclusion: The immunostaining with the anti-p63 antibody in the prostate cancer diagnosis is of considerable benefit. It made it possible to correct 11.3% of benign diagnosis in minimal malignant focus in our context. Despite the difficulties associated with the manual technique, it is possible to have an informative rate, similar to the automatic technique.
文摘This observational prospective study was conducted on 25 patients who had received a full 3-dose COVID-19 vaccination scheme with a follow-up ranging from 12 to 19 months after the last injection. The aim of the study was focused on a single biological indicator the anti-spike IgG antibody titer. The age of the patients ranged from 51 to 85 years old. 15 out 25 patients (60%) presented a comorbidity. Our data showed a persistent positive anti-spike IgG antibodies titer ranging from 105 to 5680 BAU/mL (mean: 2661 BAU/mL) in all patients. In view of these results, systematic administration of a SARS-CoV-2 vaccine booster is questionable and should be individually tailored according to the patient medical condition and the anti-spike IgG antibody level.
文摘Anti β NGF antiserum was prepared by immunizing rabbits with purified mouse β NGF. It presented immunopositivity to β NGF on Western blot, resulting in a single band approximately at the molecular weight of 14 kDa. The antiserum was further purified into anti β NGF IgG by affinity chromatography. Chicken embryonic dorsal root ganglia (DRG) were cultured to test the biological activities of β NGF and its antibody.
文摘Primary biliary cirrhosis(PBC) is a chronic,progressive,cholestatic,organ-specific autoimmune disease of unknown etiology.It predominantly affects middle-aged women,and is characterized by autoimmune-mediated destruction of small-and medium-size intrahepatic bile ducts,portal inflammation and progressive scarring,which without proper treatment can ultimately lead to fibrosis and hepatic failure.Serum autoantibodies are crucial tools for differential diagnosis of PBC.While it is currently accepted that antimitochondrial antibodies are the most important serological markers of PBC,during the last five decades more than sixty autoantibodies have been explored in these patients,some of which had previously been thought to be specific for other autoimmune diseases.
基金Supported by PENED 2003(03E_66)from the Greek Secretariat of Research and Technology to Theodoropoulos PA
文摘AIM:To investigate possible associations of anti-nuclear envelope antibody(ANEA)with disease severity and survival in Greek primary biliary cirrhosis(PBC)patients.METHODS:Serum samples were collected at diagnosis from 147 PBC patients(85%female),who were followed-up for a median 89.5 mo(range 1-240).ANEA were detected with indirect immunofluorescence on 1% formaldehyde fixed Hep2 cells,and anti-gp210 antibodies were detected using an enzyme linked immunosorbent assay.Findings were correlated with clinical data,histology,and survival.RESULTS:ANEA were detected in 69/147(46.9%) patients and 31/147(21%)were also anti-gp210 positive.The ANEA positive patients were at a more advanced histological stage(Ⅰ-Ⅱ/Ⅲ-Ⅳ56.5%/43.5% vs 74.4%/25.6%,P=0.005)compared to the ANEA negative ones.They had a higher antimitochondrial antibodies(AMA)titer(≤1:160/>1:160 50.7%/49.3%vs 71.8%/28.2%,P=0.001)and a lower survival time(91.7 ±50.7 mo vs 101.8±55 mo,P=0.043).Moreover,they had more advanced fibrosis,portal inflammation,interface hepatitis,and proliferation of bile ductules(P =0.008,P=0.008,P=0.019,and P=0.027,respectively).They also died more frequently of hepatic failure and/or hepatocellular carcinoma(P=0.016).ANEA positive,anti-gp210 positive patients had a difference in stage(Ⅰ-Ⅱ/Ⅲ-Ⅳ54.8%/45.2%vs 74.4%/25.6%,P= 0.006),AMA titer(≤1:160/>1:160 51.6%/48.4%vs 71.8%/28.2%,P=0.009),survival(91.1±52.9 mo vs 101.8±55 mo,P=0.009),and Mayo risk score(5.5 ±1.9 vs 5.04±1.3,P=0.04)compared to the ANEA negative patients.ANEA positive,anti-gp210 negative patients had a difference in AMA titer(≤1:160/>1:160 50%/50%vs 71.8%/28.2%,P=0.002),stage(Ⅰ-Ⅱ/Ⅲ -Ⅳ57.9%/42.1%vs 74.4%/25.6%,P=0.033),fibrosis(P=0.009),portal inflammation(P=0.018),interface hepatitis(P=0.032),and proliferation of bile ductules(P=0.031).Anti-gp210 positive patients had a worse Mayo risk score(5.5±1.9 vs 4.9±1.7,P=0.038)than the anti-gp210 negative ones.CONCLUSION:The presence of ANEA and anti-gp210 identifies a subgroup of PBC patients with advanced disease severity and poor prognosis.
文摘AIM To analyze the clinical impact of preformed antiH LA-Cw vs antiH LA-A and/or-B donor-specific antibodies(DSA) in kidney transplantation.METHODS Retrospective study, comparing 12 patients transplanted with DSA exclusively antiH LA-Cw with 23 patients with preformed DSA antiH LA-A and/or B.RESULTS One year after transplantation there were no differencesin terms of acute rejection between the two groups(3 and 6 cases, respectively in the DSA-Cw and the DSA-A-B groups; P = 1). At one year, eG FR was not significantly different between groups(median 59 mL /min in DSA-Cw group, compared to median 51 mL /min in DSA-A-B group, P = 0.192). Moreover, kidney graft survival was similar between groups at 5-years(100% in DSA-Cw group vs 91% in DSA-A-B group, P = 0.528). The sole independent predictor of antibody mediated rejection(AMR) incidence was DSA strength(HR = 1.07 per 1000 increase in MFI, P = 0.034). AMR was associated with shortened graft survival at 5-years, with 75% and 100% grafts surviving in patients with or without AMR, respectively(Log-rank P = 0.005).CONCLUSION Our data indicate that DSA-Cw are associated with an identical risk of AMR and impact on graft function in comparison with "classical" class I DSA.
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.
文摘AIM: To identify the role of anti-pancreatic antibody (PAB) in the diagnosis of inflammatory bowel diseases (IBD) among Turkish patients, and its frequency in firstdegree relatives.METHODS: PAB and anti-Saccharomyces cerevisiae (ASCA) were examined in serum samples of 214 subjects including patients with Crohn's disease (CD, n = 64), ulcerative colitis (UC, n = 63), first-degree relatives of patients with CD (n = 25), first-degree relatives of patients with UC (n = 28),and a control group with gastrointestinal symptoms other than (IBD) (n = 34) by indirect immunofluorescence Positivity of PAB and ASCA was compared in terms of Vienna classification, disease activity and medications used.RESULTS: In terms of PAB positivity, no difference was found between patients with CD (14.1%) and UC (7.9%) however, significant difference was observed between patients with CD and subjects in the control group (P < 0.05). No difference was found between patients with CD and their relatives in terms of ASCA positivity, whereas a significant difference was found between other groups (P < 0.001). Compared to ASCA, the sensitivity of the PAB was 19% (7/37), its specificity was 93% (25/27), positive predictive value was 77% (7/9) and negative predictive value was 45% (25/55). ASCA was found with significantly higher prevalence in patients with CD activity index > 150 (P < 0.05).CONCLUSION: PAB is valuable in the diagnosis of IBD rather than CD, but cannot be used alone for diagnostic purposes. PAB is not superior to ASCA in CD diagnosis and in detecting CD among relatives of patients with CD.
文摘Summary: To study whether there was an anti-cardiac myosin antibody (AMA) in serum of pa- tients with myocardial infarction (AMI), relationship between AMA and the prognosis in patients with AMI was investigated. In 67 patients with acute AMI, AMA was assayed by ELISA and left ventricular structure and cardiac function were examined by echocardiography at the end of the first week after infarction and during a 6-month follow-up. The patients with AMI were divided into AMA-positive group and AMA-negative group. The parameters of left ventricular end-dias- tolic function and prognosis were compared between the two groups. Results showed that the AMA was positive in 18 patients with AMI, with a positive rate of 26. 87 %, while it was negative in 20 health donors. The locations of myocardial infarction in the two groups were similar. There were significant differences in Killip class I (22. 22 % vs 55. 10 %, P<0. 05), decreasing of wall motion and ventricular aneurysm (92. 85 % vs 37. 5 %, P<0.01) between the positive group and the negative group. During a 6-month follow-up, the mortality was higher in AMA positive group than in AMA negative group (38. 89% vs 10. 20 %, P<0. 05). It is concluded that AMA can be detected in serum of patients with AMI and can serve as an important autoimmune marker. The autoimmune response might take place in AMI. AMA was associated with the left ventricular re- modeling and the prognosis of AMI.
文摘Mutation of the p53 gene is a key event in the carcinogenesis of many different types of tumours. These can occur throughout the length of the p53 gene. Anti-p53 auto-antibodies are commonly produced in response to these p53 mutations. This review firstly describes the various mechanisms of p53 dysfunction and their association with subsequent carcinogenesis. Following this, the mechanisms of induction of anti-p53 auto-antibody production are shown, with various hypotheses for the discrepancies between the presence of p53 mutation and the presence/absence of anti-p53 auto-antibodies. A systematic review was performed with a descriptive summary of key findings of each anti-p53 auto-antibody study in all cancers published in the last 30 years. Using this, the cumulative frequency of anti-p53 autoantibody in each cancer type is calculated and then compared with the incidence of p53 mutation in each cancer to provide the largest sample calculation and correlation between mutation and anti-p53 auto-antibody published to date. Finally, the review focuses onthe data of anti-p53 auto-antibody in colorectal cancer studies, and discusses future strategies including the potentially promising role using anti-p53 auto-antibody presence in screening and surveillance.
基金Supported by a Grant-in-Aid for Scientific Research(C)from the Ministry of Education,Culture,Sports,Science,and Technology,Japan,No.17K10460(to Aung W)
文摘AIM To investigate near-infrared photoimmunotherapeutic effect mediated by an anti-tissue factor(TF) antibody conjugated to indocyanine green(ICG) in a pancreatic cancer model.METHODS Near-infrared photoimmunotherapy(NIR-PIT) is a highly selective tumor treatment that utilizes an antibody-photosensitizer conjugate administration, followed by NIR light exposure. Anti-TF antibody 1849-ICG conjugate was synthesized by labeling of rat IgG2 b anti-TF monoclonal antibody 1849(anti-TF 1849) to a NIR photosensitizer,ICG. The expression levels of TF in two human pancreatic cancer cell lines were examined by western blotting. Specific binding of the 1849-ICG to TF-expressing BxPC-3 cells was examined by fluorescence microscopy. NIR-PITinduced cell death was determined by cell viability imaging assay. In vivo longitudinal fluorescence imaging was used to explore the accumulation of 1849-ICG conjugate in xenograft tumors. To examine the effect of NIRPIT, tumor-bearing mice were separated into 5 groups:(1) 100 μg of 1849-ICG i.v. administration followed by NIR light exposure(50 J/cm2) on two consecutive days(Days 1 and 2);(2) NIR light exposure(50 J/cm2) only on two consecutive days(Days 1 and 2);(3) 100 μg of 1849-ICG i.v. administration;(4) 100 μg of unlabeled antiTF 1849 i.v. administration; and(5) the untreated control. Semiweekly tumor volume measurements, accompanied with histological and immunohistochemical(IHC) analyses of tumors, were performed 3 d after the 2nd irradiation with NIR light to monitor the effect of treatments. RESULTS High TF expression in BxPC-3 cells was observed via western blot analysis, concordant with the observed preferential binding with intracellular localization of 1849-ICG via fluorescence microscopy. NIR-PIT-induced cell death was observed by performing cell viability imaging assay. In contrast to the other test groups, tumor growth was significantly inhibited by NIR-PIT with a statistically significant difference in relative tumor volumes for 27 d after the treatment start date [2.83 ± 0.38(NIR-PIT) vs 5.42 ± 1.61(Untreated), vs 4.90 ± 0.87(NIR), vs 4.28 ±1.87(1849-ICG), vs 4.35 ± 1.42(anti-TF 1849), at Day 27, P < 0.05]. Tumors that received NIR-PIT showed evidence of necrotic cell death-associated features upon hematoxylin-eosin staining accompanied by a decrease in Ki-67-positive cells(a cell proliferation marker) by IHC examination.CONCLUSION The TF-targeted NIR-PIT with the 1849-ICG conjugate can potentially open a new platform for treatment of TF-expressing pancreatic cancer.
文摘The suppressive effect of anti-KDR antibody against VEGF on proliferation of hemangioma-derived vascular endothelial cells （HVECs） was investigated. HVECs from one case of hemangioma in proliferative phase were cultured. Both primary culture and sub-culture were conducted in M199 medium. The HVECs of passage 3 were divided into 4 groups based on the concentrations of anti-KDR antibody. Cell count was performed and inhibitory rate of HVECs was measured before and 9 days after interference. The results showed that the number of HVECs in the anti-KDR anti- body-treated groups was significantly decreased and the inhibitory rate of HVECs by anti-KDR antibody （50, 10 and 2 μg/mL） was 84%, 63% and 39% respectively at 9th day after interference, with the difference being significant. In the control group, the number of HVECs was increased significantly. In was concluded that the anti-KDR antibody could suppress the activity of VEGF through blocking the KDR, indicating the potential clinical applications of anti-KDR antibody in the treatment of hemangioma.
基金Supported by Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences,Internal Research Grant of University of Debrecen and the IOIBD Research Grant
文摘AIM: To assess the prevalence and stability of different antiphospholipid antibodies(APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases(IBD) patients.METHODS: About 458 consecutive patients [Crohn's disease(CD): 271 and ulcerative colitis(UC): 187] were enrolled into a follow-up cohort study in a tertiary IBD referral center in Hungary. Detailed clinical phenotypes were determined at enrollment by reviewing the patients' medical charts. Disease activity, medical treatment and data about evolvement of complications or surgical interventions were determined prospectively during the follow-up. Disease course(development f complicated disease phenotype and need for surgery),occurrence of thrombotic events, actual state of diseaseactivity according to clinical, laboratory and endoscopic scores and accurate treatment regime were recorded during the follow-up,(median, 57.4 and 61.6 mo for CD and UC). Sera of IBD patients and 103 healthy controls(HC) were tested on individual anti-β2-Glycoprotein-I(anti-β2-GPI IgA/M/G), anti-cardiolipin(ACA IgA/M/G)and anti-phosphatidylserine/prothrombin(anti-PS/PT IgA/M/G) antibodies and also anti-Saccharomyces cerevisiae antibodies(ASCA IgA/G) by enzyme-linked immunosorbent assay(ELISA). In a subgroup of CD(n = 198) and UC patients(n = 103), obtaining consecutive samples over various arbitrary timepoints during the disease course, we evaluated the intraindividual stability of the APLA status. Additionally,we provide an overview of studies, performed so far, in which significance of APLAs in IBD were assessed.RESULTS: Patients with CD had significantly higher prevalence of both ACA(23.4%) and anti-PS/PT(20.4%) antibodies than UC(4.8%, p < 0.0001 and10.2%, p = 0.004) and HC(2.9%, p < 0.0001 and15.5%, p = NS). No difference was found for the prevalence of anti-β2-GPI between different groups(7.2%-9.7%). In CD, no association was found between APLA and ASCA status of the patients.Occurrence of anti-β2-GPI, ACA and anti-PS/PT was not different between the group of patients with active vs inactive disease state according to appropriate clinical, laboratory and endoscopic scores in CD as well as in UC patients. All subtypes of anti-β2-GPI and ACA IgM status were found to be very stable over time, in contrast ACA IgG and even more ACA IgA status showed significant intraindividual changes.Changes in antibody status were more remarkable in CD than UC(ACA IgA: 49.9% vs 23.3% and ACA IgG:21.2% vs 5.8%). Interestingly, 59.1% and 30.1% of CD patients who received anti-TNF therapy showed significant negative to positive changes in ACA IgA and IgG antibody status respectively. APLA status was not associated with the clinical phenotype at diagnosis or during follow-up, medical therapy, or thrombotic events and it was not associated with the probability of developing complicated disease phenotype or surgery in a Kaplan-Meier analysis.CONCLUSION: The present study demonstrated enhanced formation of APLAs in CD patients. However,presence of different APLAs were not associated with the clinical phenotype or disease course.
文摘Dendritic cells(DCs) are professinal antigen-presenting cells with the ability to initiate primary Tcell responses. While it iswell known that inflammatory stimuli induce the functional maturation of immature DCs, whether adhesion molecule selectins regulate DCmaturation is poorly understood. Using anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb) that blocks the adhesionof P-, E-, and L-selectin, we demonstrate herein that selectins play important role in stimulating functional maturation of immature DCs.Immature DCs are generated from human cord blood CD34+hematopoietic stem/progenitor cells that were cultured in the presence of stemcell factor, Fms-like tyrosine-kinase-3 ligand, granulocyte-macrophage colony stimulating factor, and transform growth factor-β1. Whenstimulated with tumor necrosis factor-alpha(TNF-α), immature DCs differentiated into mature DCs, producing increased levels of costim-ulatory molecules and interleukin (IL)-12 and obtaining the ability to potently activate naive Tcells. Interestingly, in contrast to matureDCs derived from TNF-α-induced immature DC cultures without PsL-EGFmAb, immature DCs treated with PsL-EGFmAb for7 days werecompletely blocked their maturation, as evidenced by decreased expression of costimulatory molecules CD80, CD86, and CD83, inhibi-ted production of IL-12, and inability to activate naive Tcellsin vitro. Thus, blockade of selectins using PsL-EGFmAb will prove to bea valuable tool for the study of the molecuar mechanisms of DC maturation, as well as for the prevention and treatment of DC-mediated au-toimmunity.
基金supported in part by Chinese National Major Project for New Drug Innovation (2008ZX09312-020,2009ZX09503-014,2012ZX09303012 and 2013ZX09402301)National Key Technology Support Program (2014BAI09B12)+1 种基金Beijing Municipal Science and Technology Commission Major Project for New Drug Innovation (Z111102071011001)Beijing Municipal Science and Technology Commission Project for Beijing Key Laboratory (Z121102009212055)
文摘Objective： This study was designed to determine the safety, pharmacokinetics and biologic effects of a humanmouse chimeric anti-CD20 monoclonal antibody （SCT400） in Chinese padents with CD20-positive B-cell non- Hodgkin＇s lymphoma （CD20 B-cell NHL）. SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians. Methods： Fifteen patients with CD20＋ B-cell NHL received dose-escalating SCT400 infusions （250 mg/m2： n=3; 375 mg/m2： n=9; 500 mg/m2： n=3） once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacoklnetics and pharmacodynamics analyses. Results： No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 ncutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer （NK） cell count or immunoglobulin levels. No patient developed anti- SCT400 antibodies during the course of the study. SCT400 serum half-life （Tin）, maximum concentration （Cmax and area under the curve （AUC） generally increased between the first and fourth infusions （P〈0.05）. At the 375 mg/m2 dose, the T1/2 was 122.5±46.7 h vs. 197.0,75.0 11, respectively, and the Cmax was 200.6±20.2 pg/mL vs. 339.1±71.0 ng/mL, respectively. From 250 mg/m2 to 500 mg/m2, the Cmax and AUC increased significantly in a dose-dependent manner （P〈0.05）. Patients with a high tumor burden had markedly lower serum SCT400 concenmations compared with those without or with a low tumor burden. Of the 9 assessable patients, 1 achieved complete response and 2 achieved partial responses. Conclusions; SCT400 is well-tolerated and has encouraging preliminary efficacy in Chinese patients with CD20＋ B-cell NHL.
基金Supported by the Development of New Faculty Staff,Ratchadaphiseksomphot Endowment Fund to Sintusek PThe Special Task Force for Activating Research in Immune Response in Children with Chronic Liver Diseases and Children after Liver Transplantation,Chulalongkorn University and King Chulalongkorn Memorial Hospital,Bangkok,Thailand to Sintusek P+1 种基金the Research Chair Grant from the National Science and Technology Development Agency,No.P-15-50004 to Poovorawan YThe Center of Excellence in Clinical Virology,Chulalongkorn Unversity and King Chulalongkorn Memorial Hospital,No.GCE 5900930-005 to Poovorawan Y
文摘AIM To assess the seroprevalence of hepatitis B virus(HBV) immunity among previously vaccinated pediatric liver transplant recipients and present a case report of de novo hepatitis B infection after liver transplantation.METHODS This study focused on children with chronic liver diseases who received primary hepatitis B immunization and had a complete dataset of anti-HBs before and after liver transplantation between May 2001 and June 2017. Medical records were retrospectively reviewed for potential factors relating to HBV immunity loss. RESULTS In total, 50 children were recruited. The mean time from liver transplantation to anti-HBs testing was 2.53 ± 2.11 years. The mean anti-HBs levels before and after liver transplantation were 584.41 ± 415.45 and 58.56 ± 6.40 IU/L, respectively. The rate of nonimmunity(anti-HBs < 10 IU/L) in the participants was 46%(n = 26) at one year, 57%(n = 7) at two years and 82%(n = 17) at > three years following liver transplantation. The potential factors relating to HBV immunity loss after liver transplantation were identified as anti-HBs(P = 0.002), serum albumin(P = 0.04), total bilirubin(P = 0.001) and direct bilirubin(P = 0.003) before liver transplantation. A five-year-old boy with biliary cirrhosis received 4 doses of HBV vaccine with an anti-HBs titer of > 1000 IU/L and underwent liver transplantation; his anti-HBc-negative father was the donor. After liver transplantation, the boy had stenosis of the hepatic artery up to the inferior vena cava anastomosis and underwent venoplasty three times. He also received subcutaneous injections of enoxaparin for 5 mo and 20 transfusions of blood components. Three years and ten months after the liver transplantation, transaminitis was detected with positive tests for HBs Ag, HBe Ag, and anti-HBc(2169.61, 1706 and 8.45, respectively; cutoff value: < 1.00) and an HBV viral load of 33212320 IU/mL.CONCLUSION The present study showed that loss of hepatitis B immunity after liver transplantation is unexpectedly common. In our case report, despite high levels of antiHBs prior to transplantation, infection occurred at a time when, unfortunately, the child had lost immunity to hepatitis B after liver transplantation.
基金This study was supported by grants of Czech Ministry of Health (VU 96/69).
文摘Objective To study the findings of serum antibodies against annexin V, prothrombin, ph-inositol, ph-acid, ph-ethanolamine, ph-serine, ph-glycerol, cardiolipin, and beta2-glycoprotein I and analyze the trophoblast annexin V receptors Methods Sera from 156patients aged 26-41 years with recurrent pregnancy loss （3-7 times） were investigated. Eighty-four fertile healthy women aged 24-38 years were included in a control group. ELISA methods were used for detecting a panel of sera anti-phospholipid antibodies. Immunolocalization of annexin V receptors in 143 trophoblast specimens of 156 patients was investigated by the immunofluorescence technique using Annexin V-FITC, Apoptosis and Annexin V-CY3 commercial kits. Results Positivity for anti-phospholipid antibodies mainly against ph-serine, ph- ethanolamine, and ph-inositol was found together in 80. 8%（126 out of 156 patients）, anti-prothrombin antibodies in 12% （18）, and anti-annexin V antibodies in 13. 5% （21） women. No significant levels of anti-phospholipid antibodies were found in 6 controls. Placenta immunohistopathology also exhibited some changes manifested by the presence of apoptotic and necrotic cells in trophoblast, and very few microthrombotization in some intervillous spaces. Conclusion Our detailed study demonstrated the prevalence of majority of antiphospholipid antibodies as a high risk factor for repeated reproductive failure. Very low microthrombosis in placentas could be explained by the changes of haemocoagulation properties out of uterus.
