Chuiwen Deng

Clinical characteristics of immunoglobulin G4–related disease: a prospective study of 118 Chinese patients

OBJECTIVE To characterize the clinical features of IgG4-related disease (IgG4-RD) in China. METHODS A prospective cohort study of IgG4-RD was carried out in Peking Union Medical College Hospital between 2011 and 2013. Patients with newly diagnosed IgG4-RD were enrolled. RESULTS A total of 118 patients with IgG4-RD were enrolled, including 82 males and 36 females, aged 53.1 (s.d. 13.6) years. The most common symptom at onset was lacrimal gland swelling (38/32.2%). A range of organs were involved: 77 patients (65.3%) had lymphadenopathy, 76 (64.4%) had sialadenitis, 60 (50.8%) had dacryoadenitis, 45 (38.1%) had autoimmune pancreatitis, 32 (27.1%) had pulmonary involvement, 31 (26.3%) had periaortitis/retroperitoneal fibrosis, 29 (35.4% of male patients) had prostatitis and 29 (24.6%) had renal involvement. In addition, there were 21 (17.8%) cases of sclerosing cholangitis, 15 (12.7%) of sinusitis and 10 (8.5%) of inflammatory pseudotumour. Uncommon manifestations included mediastinal fibrosis, skin involvement, sclerosing thyroiditis, hypophysitis, orchitis and colitis. Multiple organ involvement was observed in 93 patients, whereas only 4.2% had only a single organ involved. A history of allergy was reported in 73 (61.9%) patients. The serum IgG4 level was elevated in 97.5% and was correlated with the number of organs involved. Most patients were treated with glucocorticoids alone or in combination with immunosuppressive drugs, and the majority usually improved within 3 months. CONCLUSION IgG4-RD is a systemic inflammatory and sclerosing disease. Parotid and lacrimal involvement (formerly called Mikuliczs disease), lymphadenopathy and pancreatitis are the most common manifestations. Patients with IgG4-RD showed favourable responses to treatment with glucocorticoids and immunosuppressive agents.

Genetic Association Study of TNFAIP3, IFIH1, IRF5 Polymorphisms with Polymyositis/Dermatomyositis in Chinese Han Population

Background Single-nucleotide polymorphisms (SNPs) in the TNFAIP3, IFIH1, and IRF5 genes have been associated with several auto-inflammation diseases, while the susceptibility between these genes and idiopathic inflammatory myopathies (IIMs) were not reported. This study aimed to investigate whether TNFAIP3, IFIH1, and IRF5 gene polymorphisms confer susceptibility for the IIMs in Chinese Han population. Methods A large case–control study of Chinese subjects with polymyositis (PM) (n = 298) and dermatomyositis (DM) (n = 530) was accomplished. 968 healthy and ethnically matched controls were available for comparison. Six SNPs in the TNFAIP3 region (rs2230926 and rs5029939), the IFIH1 gene (rs1990760 and rs3747517) and the IRF5 region (rs4728142 and rs729302) were assessed and genotyped using the Sequenom MassArray iPLEX platform. Results Our study indicated a strong allele association was observed in PM/DM and PM patients for rs2230926 (OR: 1.61, 95%CI: 1.20–2.16, Pc = 7.5×10−3; OR: 1.88, 95%CI: 1.30–2.74, Pc = 4.0×10−3, respectively) and rs5029939 (OR: 1.64, 95%CI: 1.21–2.21, Pc = 6.0×10−3; OR: 1.88, 95%CI: 1.28–2.76, Pc = 5.5×10−3,respectively). And rs2230926 and rs5029939 were significantly associated with interstitial lung disease (ILD) in PM/DM and PM patients (Pc = 0.04 and Pc = 0.016; Pc = 0.02 and Pc = 0.03, respectively). In addition, rs4728142 allele and genotype had significant association with PM/DM patients (Pc = 0.026 and Pc = 0.048, respectively). Further analysis with three logistic regression genetic models revealed statistically significant difference in the genotypic distribution in the PM/DM, PM or DM patients when the additive and dominant models were used. Conclusions This was the first study to reveal TNFAIP3 and IRF5 polymorphisms were associated with PM/DM patients or these patients with ILD, indicating that TNFAIP3 and IRF5 might be the susceptibility gene for PM/DM patients in Chinese Han population.

Meta-Analysis: Diagnostic Accuracy of Anti-Carbamylated Protein Antibody for Rheumatoid Arthritis

Objective The anti-carbamylated protein (CarP) antibody is a novel biomarker that might help in the diagnosis of rheumatoid arthritis (RA). We aim to assess the diagnostic value of anti-CarP antibody for RA. Methods We systematically searched PubMed, Embase, the Cochrane Library, Web of Science, and Scopus for studies published by December 15, 2015. Studies in any language that evaluated the utility of the anti-CarP antibody in the diagnosis of RA in which healthy donors or patients without arthritis or arthralgia served as controls were included. Two investigators independently evaluated studies for inclusion, assessed study quality and abstracted data. A bivariate mixed-effects model was used to summarize the diagnostic indexes from 7 eligible studies. Results The pooled sensitivity, specificity, and positive and negative likelihood ratios for anti-CarP antibody were 42% (95% CI, 38% to 45%), 96% (95% CI, 95% to 97%), 10.2 (95% CI, 7.5 to 13.9), and 0.61 (95% CI, 0.57 to 0.65), respectively. The summary diagnostic odds ratio was 17 (95% CI, 12 to 24), and the area under summary receiver operator characteristic curve was 80% (95% CI, 77% to 84%). Conclusion Anti-CarP antibody has a moderate value in the diagnosis of RA with high specificity but relatively low sensitivity.

Exploring Serological Classification Tree Model of Active Pulmonary Tuberculosis by Magnetic Beads Pretreatment and MALDI‐TOF MS Analysis

Pulmonary tuberculosis (TB) is an infectious disease disturbing status of public health, and accurate diagnosis of TB would effectively help control the disturbance. Our study tried to establish a classification tree model that distinguished active TB from non‐TB individuals. We used matrix‐assisted laser desorption/ionization time of flight mass spectrometry (MALDI‐TOF MS) combined with weak cationic exchange (WCX) magnetic beads to analyse 178 serum samples containing 75 patients with active TB and 103 non‐TB individuals (43 patients with common pulmonary diseases and 60 healthy controls). Samples were randomly divided into a training set and a test set. Statistical softwares were applied to construct this model. An amount of 48 differential expressed peaks (P < 0.05) were identified by the training set, and our model was set up by three of them, m/z 7626, 8561 and 8608. This model can discriminate patients with active TB from patients with non‐TB with a sensitivity of 98.3% and a specificity of 84.4%. The test set was used to verify the performance, which demonstrated good sensitivity and specificity: 85.7% and 83.3%, respectively. Differential expressed peaks between smear‐positive and smear‐negative active TB also have been analysed. It came out that m/z 8561 and 8608 not only acted as vital factors in the pathogenesis of active TB but also played an important role in regulating different active TB status. In conclusion, MALDI‐TOF MS combined with WCX magnetic beads was a powerful technology for constructing classification tree model, and the model we built could serve as a potential diagnostic tool for active TB.

Establishing a serologic decision tree model of extrapulmonary tuberculosis by MALDI-TOF MS analysis.

Matrix-assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS) combined with weak cationic exchange (WCX) magnetic beads was used to establish a decision tree model that distinguished extrapulmonary tuberculosis (EPTB) from non-EPTB individuals. Eight-one patients with EPTB and 112 non-EPTB individuals (72 disease controls and 40 healthy controls) were involved in this study. The model was set up by 5 of 19 differentially expressed peaks (P < 0.05), m/z 4100, 4310, 6093, 8605, and 14,019. This model can discriminate patients with EPTB from non-EPTB with a sensitivity of 97.7% and a specificity of 84.1%. The test set verified that this model had good sensitivity and specificity: 94.4% and 83.6%, respectively. In conclusion, MALDI-TOF MS combined with WCX magnetic beads is a powerful technology for constructing a decision tree model and the model we built could serve as a potential diagnostic tool for EPTB.

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.

Risk of malignancy in ankylosing spondylitis: a systematic review and meta-analysis.

Current knowledge about the overall and site-specific risk of malignancy associated with ankylosing spondylitis (AS) is inconsistent. We conducted a systematic review and meta-analysis to address this knowledge gap. Five databases (PubMed, EMBASE, Web of Science, the Cochrane library and the virtual health library) were systematically searched. A manual search of publications within the last 2 years in key journals in the field (Annals of the Rheumatic Diseases, Rheumatology and Arthritis & rheumatology) was also performed. STATA 11.2 software was used to conduct the meta-analysis. After screening, twenty-three studies, of different designs, were eligible for meta-analysis. AS is associated with a 14% (pooled RR 1.14; 95% CI 1.03–1.25) increase in the overall risk for malignancy. Compared to controls, patients with AS are at a specific increased risk for malignancy of the digestive system (pooled RR 1.20; 95% CI 1.01 to 1.42), multiple myelomas (pooled RR 1.92; 95% CI 1.37 to 3.69) and lymphomas (pooled RR 1.32; 95% CI 1.11 to 1.57). On subgroup analysis, evidence from high quality cohort studies indicated that AS patients from Asia are at highest risk for malignancy overall. Confirmation of findings from large-scale longitudinal studies is needed to identify specific risk factors and to evaluate treatment effects.

Diagnostic Potential of Zymogen Granule Glycoprotein 2 Antibodies as Serologic Biomarkers in Chinese Patients With Crohn Disease.

Abstract The need for reliable biomarkers for distinguishing Crohn disease (CD) from ulcerative colitis (UC) is increasing. This study aimed at evaluating the diagnostic potential of anti-GP2 antibodies as a biomarker in Chinese patients with CD. In addition, a variety of autoantibodies, including anti-saccharomyces cerevisiae antibodies (ASCA), perinuclear anti-neutrophil cytoplasmic antibodies (PANCA), anti-intestinal goblet cell autoantibodies (GAB), and anti-pancreatic autoantibodies (PAB), were evaluated. A total of 91 subjects were prospectively enrolled in this study, including 35 patients with CD, 35 patients with UC, 13 patients with non-IBD gastrointestinal diseases as disease controls (non-IBD DC), and 8 healthy controls (HC). The diagnosis of IBD was determined based on the Lennard-Jones criteria, and the clinical phenotypes of the IBD patients were determined based on the Montreal Classification. Anti-GP2 IgG antibodies were significantly elevated in patients with CD, compared with patients with UC (P = 0.0038), HC (P = 0.0055), and non-IBD DC (P = 0.0063). The prevalence of anti-GP2 IgG, anti-GP2 IgA and anti-GP2 IgA, or IgG antibodies in patients with CD was 40.0%, 37.1%, and 54.3%, respectively, which were higher than those in non-IBD DC (anti-GP2 IgG, 15.4%; anti-GP2 IgA, 7.7%; and anti-GP2 IgA or IgG, 23.1%) and those in patients with UC (anti-GP2 IgG, 11.4%; anti-GP2 IgA, 2.9%; and anti-GP2 IgA or IgG, 14.3%). For distinguishing CD from UC, the sensitivity, specificity, positive predictive value (PPV) and positive likelihood ratios (LR+) were 40%, 88.6%, 77.8%, and 3.51 for anti-GP2 IgG, 37.1%, 97.1%, 92.9%, and 13.0 for anti-GP2 IgA, and 54.3%, 85.3%, 79.2%, and 3.69 for anti-GP2 IgA or IgG. For CD diagnosis, the combination of anti-GP2 antibodies with ASCA IgA increased the sensitivity to 68.6% with moderate loss of specificity to 74.3%. Spearmans rank of order revealed a significantly positive correlation of anti-GP2 IgG with ileocolonic location of disease (L3) (P = 0.043) and a negative correlation of anti-GP2 IgA with biologic therapy (P = 0.012). Our findings suggest that anti-GP2 antibodies could serve as a biomarker for distinguishing patients with CD from patients with UC, and the combination of anti-GP2 antibodies with ASCA IgA may improve the predictive power.

Establishment of a serum IgG4 cut-off value for the differential diagnosis of IgG4-related disease in Chinese population.

Abstract Objective: This study was performed to better know diagnosis associated with serum IgG4 concentration, and to explore the possibility for development of a serum IgG4 for IgG4-related disease (IgG4-RD) in Chinese populations. Methods: We studied retrospectively 497 IgG4 serum subclass measurements from Peking Union Medical College Hospital during the four-year period, including 242 IgG4-RD, 130 other diseases and 125 healthy individuals. Results: Serum IgG4 concentrations were significantly higher in IgG4-RD than in other pathologies (1662.9 ± 3760.9 mg/L, p < 0.001) and healthy individuals (538.2 ± 458.6 mg/L, p < 0.001). There were no significant differences in serum IgG4 level between other pathologies group and healthy individuals (p = 0.075). Among the 242 IgG4-RD patients analyzed, serum IgG4 concentrations were normal in 46 patients (19.0%). We found 32 patients (24.6%) with elevated serum IgG4 levels among the 130 patients who suffered from other pathologies. There were seven (5.6%) with serum IgG4 over 1350 mg/L in healthy individuals. The ROC curve analysis revealed that the optimal sensitivity and specificity were 80.0% and 88.2%, respectively, at the concentration of 1575 mg/L for Chinese patients. Conclusions: Our study demonstrated that serum IgG4 elevation was not specific of IgG4-RD. Further studies are needed to define the sensibility and specificity of IgG4 values for the diagnosis of IgG4-RD.

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.