Xiaoting Wen

Evaluation of the diagnostic potential of antibodies to beta2-glycoprotein 1 domain 1 in Chinese patients with antiphospholipid syndrome.

In this study, we evaluated the clinical performance of anti-β2-glycoprotein 1 domain 1 antibodies (aβ2GP1-D1) in the diagnosis of antiphospholipid syndrome (APS). Sera from 229 subjects were tested, including 35 patients with primary APS, 51 patients with APS associated to other diseases, 30 patients with non-APS thrombosis, 32 patients with non-APS pregnancy-related morbidity, 42 patients with systemic lupus erythematosus, and 39 healthy controls (HC). Serum IgG aβ2GP1-D1, IgG/IgM anti-cardiolipin (aCL) and IgG/IgM aβ2GP1 were measured by a chemiluminescence assay. The levels of IgG aβ2GP1-D1 were significantly increased in patients with APS, compared with disease controls and HCs (p < 0.001). Significant correlation was identified between IgG aβ2GP1-D1 and IgG aβ2GP1 (p < 0.0001), indicating IgG aβ2GP1-D1 were the predominant domain-specific antibodies in IgG aβ2GP1 family. Importantly, aβ2GP1-D1, but not aβ2GP1 non-D1, was significantly correlated with thrombotic events. Interestingly, no significant correlation between IgG aβ2GP1-D1 and obstetric complications was observed. Additionally, significantly higher levels of IgG aβ2GP1-D1 were found in patients with triple aPL positivity, compared with patients with double and single aPL positivity. Our findings suggest a potential role of IgG aβ2GP1-D1 in identifying APS patients with high risk of thrombosis, shedding insight on the introduction of IgG aβ2GP1-D1 in China.

Association between MEFV Mutations M694V and M680I and Behçet's Disease: A Meta-Analysis.

Objective Several studies have identified an association between Behçet’s disease (BD) and mutations in the Mediterranean fever (MEFV) gene, which was originally linked to the autosomal recessive disease, Familial Mediterranean fever. However, no consensus has been reached. Here, a meta-analysis was conducted on published data to comprehensively evaluate this relationship. Methods Literature searches were performed in Pubmed, Embase, the Web of Science, and HuGE Navigator databases, in order to identify studies pertaining to the association between MEFV mutations and BD. Two investigators independently extracted and evaluated the data from eligible studies. The association between MEFV mutations (M694V, M680I, and E148Q) and BD was estimated overall by the odds ratio (OR) and 95% confidence intervals (95% CI). Further analysis was conducted with STATA 12.0 software (Stata Corp.; College Station, TX). Results Eligible studies (n=8) included genotyping data obtained from 2538 BD patients and 2792 healthy controls. Of the three mutations, M694V (pooled OR: 2.60, 95% CI: 2.02-3.34) and M680I (pooled OR: 1.74, 95% CI: 1.23-2.46) were found to be associated with BD in the overall analysis. The third mutation, E148Q, however, was not found to be linked with BD (pooled OR: 1.26, 95% CI: 0.69-2.31). Subgroup analysis furthermore revealed that M694V and M680I were risk loci for BD specifically in Turkish patients. Conclusions The meta-analysis confirmed that MEFV mutations M694V and M680I were associated with BD. Additional studies from other ethnic populations and functional experiments are necessary to determine the extent to which the MEFV gene underlies the development of BD.

Meta-analysis of anti-muscarinic receptor type 3 antibodies for the diagnosis of Sjögren syndrome.

Purpose To conduct a meta-analysis to evaluate the diagnostic value of anti-muscarinic receptor type 3 (M3R) antibodies in Sjögren syndrome (SS). Methods Two databases, PUBMED and the Cochrane Library, were systematically searched. Approximately 2,000 participants from several studies were included in this research. STATA 11.2 software and Meta-DiSc 1.4 was used to conduct the meta-analysis. Results Eleven studies were included in the meta-analysis. The pooled DOR was 13.00 (95% CI, 6.00–26.00). The sensitivity was 0.43 (95% CI, 0.28–0.58) and the specificity was 0.95 (95%CI, 0.91–0.97). The LR+ and LR- were 7.90 (95% CI, 4.70–13.40), 0.61 (95% CI, 0.46–0.79), respectively. The AUC was 0.89 (95% CI, 0.86–0.92). Conclusion The anti-M3R antibody had high specificity but relatively low sensitivity for the diagnosis of SS.

Assessment of anti-MDA5 antibody as a diagnostic biomarker in patients with dermatomyositis-associated interstitial lung disease or rapidly progressive interstitial lung disease

Anti-melanoma differentiation-associated protein 5 (MDA5) antibody have been found in dermatomyositis (DM)-associated interstitial lung disease (DM-ILD) and DM-associated rapidly progressive ILD (DM-RPILD). Due to the conflicting results regarding the association between anti-MDA5 antibody and DM-ILD or DM-RPILD and the diagnostic value of this antibody for DM-ILD and DM-RPILD, we performed this meta-analysis. A systematic search was performed to identify studies published to January 14, 2017. Sixteen publications with 491 DM with ILD versus 605 DM without ILD, as well as eighteen publications with 186 DM with RPILD and 790 DM without RPILD were included. The pooled sensitivity, specificity, and area under the curve (AUC) values of anti-MDA5 antibody for DM-ILD were 0.47 (95% CI: 0.37-0.57), 0.96 (95% CI, 0.92-0.97), and 0.90 (95% CI: 0.88-0.93), respectively, with a low sensitivity value. The pooled sensitivity, specificity, and AUC values were 0.83 (95% CI: 0.77-0.88), 0.86 (95% CI: 0.80-0.91), and 0.87 (95% CI: 0.84-0.90) for DM with RPILD versus without RPILD with good sensitivity and specificity values. Trial sequential analysis showed sufficient evidence to support that anti-MDA5 antibody was associated with DM-ILD and DM-RPILD. The statistical power of this study calculated using G*Power version 3.1.9.2 was more than 99% (α = 0.05). Taken together, these findings suggest that anti-MDA5 antibody has a potential useful ability as a noninvasive biomarker in the diagnosis of RPILD in patients with DM.Anti-melanoma differentiation-associated protein 5 (MDA5) antibody have been found in dermatomyositis (DM)-associated interstitial lung disease (DM-ILD) and DM-associated rapidly progressive ILD (DM-RPILD). Due to the conflicting results regarding the association between anti-MDA5 antibody and DM-ILD or DM-RPILD and the diagnostic value of this antibody for DM-ILD and DM-RPILD, we performed this meta-analysis. A systematic search was performed to identify studies published to January 14, 2017. Sixteen publications with 491 DM with ILD versus 605 DM without ILD, as well as eighteen publications with 186 DM with RPILD and 790 DM without RPILD were included. The pooled sensitivity, specificity, and area under the curve (AUC) values of anti-MDA5 antibody for DM-ILD were 0.47 (95% CI: 0.37–0.57), 0.96 (95% CI, 0.92–0.97), and 0.90 (95% CI: 0.88–0.93), respectively, with a low sensitivity value. The pooled sensitivity, specificity, and AUC values were 0.83 (95% CI: 0.77–0.88), 0.86 (95% CI: 0.80–0.91), and 0.87 (95% CI: 0.84–0.90) for DM with RPILD versus without RPILD with good sensitivity and specificity values. Trial sequential analysis showed sufficient evidence to support that anti-MDA5 antibody was associated with DM-ILD and DM-RPILD. The statistical power of this study calculated using G*Power version 3.1.9.2 was more than 99% (α = 0.05). Taken together, these findings suggest that anti-MDA5 antibody has a potential useful ability as a noninvasive biomarker in the diagnosis of RPILD in patients with DM.

Anti-MDA5 antibody as a potential diagnostic and prognostic biomarker in patients with dermatomyositis

The presence of anti-MDA5 antibodies in serum represents an important biomarker in the diagnosis and prediction of prognosis for patients with idiopathic inflammatory myopathies (IIMs). Due to conflicting results that have been reported regarding the detection of anti-MDA5 antibodies, the goal of this study was to assess a potential association between the presence of anti-MDA5 antibodies and dermatomyositis/polymyositis (DM/PM), as well as the diagnostic and prognostic values of anti-MDA5 antibodies for DM/PM. For this, a review of literature published prior to October 15, 2016 was conducted. Eight studies with 286 PM patients and 216 healthy controls and nine studies with 628 DM patients and 221 healthy controls were selected according to specific inclusion criteria. The outcomes of these studies revealed that the presence of anti-MDA5 antibodies was associated with DM, especially CADM, and not with PM. Furthermore, the pooled sensitivity, specificity, and area under the curve (AUC) values were 0.62 (95% confidence interval (CI): 0.52–0.70), 1.00 (95% CI: 0.97–1.00), and 0.9381 for CADM patients versus healthy controls when an immunoprecipitation method was used. The presence of anti-MDA5 antibodies was also found to be significantly associated with an increased risk of death in DM (relative risk = 3.32, 95% CI: 1.65–6.67, P = 0.001). These findings suggest that anti-MDA5 antibodies correlate with DM and could be used as a biomarker in the clinical diagnosis of CADM. The presence of anti-MDA5 antibodies was also associated with poor prognosis regarding the overall survival of patients with DM.

Histopathological diagnostic value of the IgG4+/IgG+ ratio of plasmacytic infiltration for IgG4-related diseases: a PRISMA-compliant systematic review and meta-analysis.

AbstractThis article aims to perform a meta-analysis to evaluate the diagnostic value of the immunoglobulin G (IgG)4+/IgG+ ratio of plasmacytic infiltration for IgG4-related diseases.Four databases—EMBASE, ISI Web of Knowledge, PubMed, and the Cochrane Library—were systematically searched. Approximately 200 participants from several studies were included in this research. STATA 11.2 software (Stata Corporation, College Station, TX) and Meta-DiSc 1.4 (Unit of Clinical Biostatistics, Ramon y Cajal Hospital, Madrid, Spain) were used to perform the meta-analysis.Nine studies were included in the meta-analysis. The pooled diagnostic odds ratio was 18.94 [95% confidence interval (CI), 2.89–124.30]. The sensitivity was 58.80% (95% CI, 50.90–66.30) and the specificity was 90.20% (95% CI, 81.20–95.80). The positive and negative likelihood ratios were 3.12 (95% CI, 1.07–9.16) and 0.26 (95% CI, 0.09–0.70), respectively. The area under the curve of the summary receiver-operating characteristic was 0.88.To conclude, the IgG4+/IgG+ ratio of plasmacytic infiltration is modestly effective in diagnosing IgG-related disease.

Association of IL12A Expression Quantitative Trait Loci (eQTL) With Primary Biliary Cirrhosis in a Chinese Han Population.

AbstractGenome-wide association studies in European individuals have revealed that IL12A is strongly associated with primary biliary cirrhosis (PBC). However, this association was not detected in replicative studies conducted in Chinese Han and Japanese populations.To verify contributions of genetic variants of IL12A to the pathogenesis of PBC in Chinese populations, a replicative study of 22 single nucleotide polymorphisms (SNPs) around the IL12A gene locus was performed in a cohort of 586 PBC cases and 726 healthy controls. Three out of the 22 SNPs were significantly associated with PBC. The 2 SNPs with the most significant association signal were rs4679868 (P = 6.59E−05, odds ratio [OR] = 1.554 [1.253–1.927]) and rs6441286 (P = 8.00E−05, OR = 1.551 [1.250–1.924]). These 2 SNPs were strongly linked to each other (r2 = 0.981), and both were found to be significantly associated with PBC in European populations.An expression quantitative trait loci (eQTL) analysis was performed based on the observation that these 2 SNPs were located in proximity to 2 enhancers verified by luciferase reporter systems in the HEK293 cell line. The results of eQTL analysis, conducted using the publically accessible data, showed that the risk alleles of rs4679868 and rs6441286 were significantly associated with decreased expression of IL12A in lymphoblastoid cell lines derived from individuals of Chinese Han ancestry (P = 0.0031 for rs4679868 and P = 0.0073 for rs6441286). In addition, the risk alleles of the 2 SNPs were significantly associated with down-regulation of SCHIP1, a celiac disease susceptible gene, 91.5 kb upstream of IL12A.These results not only demonstrated that IL12A is associated with PBC in the Chinese Han population but also identified a potential mechanism for its involvement in the pathogenesis of PBC.

Association of FCGR2A/FCGR3A variant rs2099684 with Takayasu arteritis in the Han Chinese population

Takayasu arteritis (TA) is a chronic large-vessel vasculitis of unclear pathogenesis. A recent genome-wide association study (GWAS) has revealed that the FCGR2A/FCGR3A, EEFSEC, RPS9/LILRB3, RIPPLY2 and MLX genes confer susceptibility to TA. We investigated the linkage between presumptive TA-related genes (FCGR2A/FCGR3A, EEFSEC, RPS9/LILRB3, RIPPLY2 and MLX) and TA in the Han Chinese population. We performed a large case-control multi-center study of 412 Han Chinese TA patients and 597 ethnically matched healthy controls. Five single nucleotide polymorphisms (SNPs) were assessed and genotyped using Sequenom MassArray system (iPLEX assay, Sequenom, San Diego, CA, USA). The frequency of the rs2099684 variant G allele in the FCGR2A/FCGR3A gene was significantly higher in the TA patients than in the controls (37.5% compared with 25.4%, OR =1.77, 95% CI: 1.462.14, Pc =1.5×10-8). Similar results were observed in genotype distribution analysis and logistic regression analyses conducted using three genetic models. The allele and genotype distributions for the other polymorphisms were not significantly associated with TA among the Han Chinese patients. The SNP rs2099684 in FCGR2A/FCGR3A can be considered a genetic risk factor for TA in the Chinese Han population. These findings provide further insights into the etiopathogenesis of TA.

Evaluation of the clinical relevance of anti-annexin-A5 antibodies in Chinese patients with antiphospholipid syndrome

A hallmark feature of antiphospholipid syndrome (APS) is the presence of antiphospholipid antibodies (aPLs). Few studies have addressed the clinical relevance of anti-annexin A5 antibodies (aANXA5) in Chinese patients with APS. In this study, we evaluated the clinical performance of aANXA5 in the diagnosis of APS. Sera from 313 subjects were tested, including 170 samples from patients with APS, 104 samples from patients with non-APS diseases as disease controls (DC), and 39 healthy controls (HC). Serum IgG and IgM aANXA5 were determined by ELISA. Overall, the levels of both IgG and IgM aANXA5 were significantly increased in patients with primary APS (PAPS) and APS associated to other diseases (APSAOD) compared with DC and HC. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for IgG and IgM aANXA5 in the diagnosis of APS were 33.5 and 15.3, 99.0 and 99.0, 98.3 and 96.3, and 47.7 and 41.7%, respectively. Significant associations between IgG aANXA5 and arterial thrombotic events (OR, 2.60; 95% CI, 1.44–4.71) and between IgG aANXA5 and venous thrombotic events (OR, 2.80; 95% CI, 1.55–5.06) were identified. No correlations were identified between IgG or IgM aANXA5 and obstetric complications. Our data suggest that aANXA5 could serve as a diagnosis biomarker for patients with APS. More importantly, our data highlighted a potential role of IgG aANXA5 in identifying APS patients with high risk of thrombosis.

Clinical performance of antibodies to prothrombin and thrombin in Chinese patients with antiphospholipid syndrome: potential interest in discriminating patients with thrombotic events and non-thrombotic events.

Abstract A hallmark feature of antiphospholipid syndrome (APS) is the presence of a wide spectrum of antiphospholipid antibodies. In this study, we evaluated the clinical relevance of antibodies to prothrombin (PT) (aPT) and thrombin (aThr) in Chinese patients with APS. A total of 229 subjects were tested, including 86 patients with APS [35 patients with primary APS (PAPS), 51 patients with APS associated with other diseases (APSAOD)], 104 patients with non-APS diseases (disease controls), and 39 healthy controls. Serum IgG/IgM/IgA aPT and aThr were determined by ELISA. The levels of both IgG/IgM/IgA aPT and IgG/IgM/IgA aThr were significantly increased in patients with PAPS and APSAOD compared with patients with non-APS thrombosis and non-APS PRM, and HC. Both IgG aPT and IgG aThr exhibited promising diagnostic potentials for APS with sensitivities and specificities of 16.3 and 95.8% (IgG aPT), and 19.8 and 99.3% (IgG aThr), respectively. Importantly, both IgG aPT (OR 4.06; 95% CI 1.49–11.05) and IgG aThr (OR 4.49; 95% CI 1.62–12.45) were significantly correlated with arterial, but not venous, thrombotic events. Our findings highlighted that IgG aPT and IgG aThr could serve as promising biomarkers to identify patients at risk of arterial thrombosis in China.