Guo-Sheng Wang

Clinical and laboratory profiles of primary Sjogren's syndrome in a Chinese population: A retrospective analysis of 315 patients

To assess the clinical and laboratory features of primary Sjogrens syndrome (pSS) in a large teaching hospital in China.

Association of FAM167A-BLK rs2736340 Polymorphism with Susceptibility to Autoimmune Diseases: A Meta-Analysis

ABSTRACT Objective: The purpose of this study is to evaluate the correlation between family with sequence similarity 167A-B lymphoid tyrosine kinase (FAM167A-BLK) rs2736340 polymorphism and autoimmune diseases. Methods: Databases including PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature database (CBM) and Chinese database, Wan Fang database were used in searching eligible studies from January 1, 1966 to October 2, 2015. The odds ratios (ORs) and their 95% confidence intervals (CIs) were pooled to estimate the strength of the association. Results: A total of 25 studies with 30,217 patients and 44,754 controls were included in the meta-analysis. The overall results showed FAM167A-BLK rs2736340 T allele was a risk allele for autoimmune diseases (OR 1.36, 95% CI 1.28–1.44, p < 0.001). In the subgroup by ethnicities, the results suggested T allele was an increased risk in North America, Europe, and Asia (OR 1.33, 95% CI 1.10–1.60, p = 0.004; OR 1.26, 95% CI 1.22–1.31, p < 0.001; and OR 1.46, 95% CI 1.40–1563, p < 0.001, respectively), but not in Africa. Subgroup analysis in different genetic models (recessive, dominant, and additive) revealed significant association between rs2736340 and autoimmune diseases in Asia and North America, but not the recessive model in Europe or Africa, or the additive model in Africa. Stratification analysis by diseases suggested FAM167A-BLK rs2736340 had a positive association with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and Kawasaki disease, primary Sjogren’s syndrome (pSS), primary antiphosholipid syndrome (APS), and myositis. Conclusion: The current meta-analysis suggested that FAM167A-BLK rs2736340 polymorphism is associated with several autoimmune diseases.

clinical and immunological consequences of total glucosides of paeony treatment in Sjögren's syndrome: A randomized controlled pilot trial

BACKGROUND The total glucosides of paeony (TGP) can inhibit inflammation and alleviate symptoms in autoimmune diseases. This study investigated the clinical and immunological consequences of TGP treatment in patients with primary Sjögrens syndrome (SS). METHODS We conducted a randomized, double-blinded, placebo-controlled clinical trial in 45 patients with primary SS. Patients were randomized at 2:1 ratio to either TGP group (n=29) or placebo group (n=16) and followed up for 24weeks. The primary outocme was the European League Against Rheumatism Sjögrens Syndrome Patient Reported Index (ESSPRI). The secondary outcomes were stimulated and unstimulated salivary flow rate, Schirmers test and erythrocyte sedimentation rate (ESR), immuneglobulin (Ig), anti-nuclear antibody (ANA), anti-SSA, and anti-SSB. The proportions of B cells in peripheral blood and the levels of serum inerleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and B cell activating factor belonging to the TNF family (BAFF) were measured at baseline and at the end of follow up of 24weeks. RESULTS The average score of ESSPRI in both groups had no statistical significance at 24th week. The mean of ESSPRI in the dry-mouth part of questionnaire in patients who scored 3 to 6 points was significantly reduced in the TGP group changed from (4.81±0.60) at baseline to (4.20±1.46) (P=0.027) at week 24. Stimulated salivary flow rate increased at week 24 from (1.80±0.39) to (2.01±0.51) (P=0.031) and unstimulated salivary flow rate increased from (0.65±0.46) to (0.78±0.45) (P=0.011) in the TGP group, but the placebo group showed no significant difference. Erythrocyte sedimentation rate (ESR) was decreased significantly compared to the placebo group at 12- and 24-week from (40.9±18.0) to (29.4±12.2) (P=0.003) and (30.4±17.3) (P=0.024). The percentage of naive B cells decreased at week 24 in the TGP group from (77.34±12.20) to (64.59±15.60) (P=0.005) while memory B cells increased from (21.79±11.97) to (34.21±15.48) (P=0.006) respectively. The concentrations of TNF-α and IFN-γ decreased in the TGP group at week 24 from (32.51±26.67) to (24.22±13.56) (P=0.017) and (10.71±8.94) to (6.55±4.88) (P=0.022), respectively. No significant difference in ANA titer, anti-SSA antibodies, anti-SSB antibodies, C3 concentration or C4 concentration was observed between the two groups. CONCLUSION TGP appears to improve the glandular secreting function and decrease the level of inflammatory cytokines.

Expressão não equilibrada do receptor de hidrocarboneto arílico nos linfócitos T CCR6+ CD4+ e CD4+ CD25+ do sangue periférico na artrite reumatoide

OBJECTIVE The goal of this study was to analyze the role of aryl hydrocarbon receptor in peripheral blood CCR6+ CD4+ and CD4+ CD25+T cells of patients with rheumatoid arthritis. METHODS Flow cytometry was applied to determine the proportion of AhR positive cells in CCR6+ CD4+T, CD4+ CD25+T and peripheral blood peripheral mononuclear cells from each subject. AhR mRNA and CYP1A1 mRNA relative expression levels were tested by real-time PCR. RESULTS The percentage of AhR positive cells in peripheral blood mononuclear cells was higher in RA group than that in healthy cases [(35.23±10.71) % vs. (18.83±7.32) %, (p<0.01)]. The expression levels of AhR and CYP1A1 were both increased in patients with RA while compared to controls [(3.71±1.63) vs. (2.00±1.27), p=0.002; (2.62±2.08) vs. (0.62±0.29), p<0.01, respectively]. In RA patients, the percentage of AhR positive cells in CD4+CD25+T cells was significantly lower than that from controls [17.90(6.10±80.10)]% vs. (52.49±19.18)%, p<0.01]; In healthy controls, the percentage of AhR positive cells in CD4+CD25+T cells was significantly higher than that in CCR6+CD4+T cells, and was also significantly higher than that in PBMCs [(52.49±19.18)% vs. (23.18±5.62)% vs. (18.06±7.80)%, X2=24.03, p<0.01]; in RA patients, the percentage of AhR positive cells in CCR6+CD4+T cells was significantly increased than that in CD4+CD25+T cells and PBMCs (46.02±14.68)% vs. [17.90 (6.10±80.10)] %vs. (34.22±10.33)%, X2=38.29, p<0.01]; Nevertheless, no statistically significant relationship was found between clinical data and AhR positive cells in CCR6+CD4+T and CD4+ CD25+T cells. CONCLUSION AhR may participate in the pathological progress of RA by controlling the differentiation of Th17 and Treg cells in peripheral blood.

SAT0180 B7-H4 expression of renal tubular epithelial cells in patients with lupus nephritis

Background B7-H4 is a newly identified B7 family negative co-stimulate molecule, the expression and function of B7-H4, in the pathogenesis of lupus nephritis (LN) is still unclear. Objectives To investigate the expression of B7-H4 in patients with LN and the function of renal tubular epithelial cells (TECs)-associated B7-H4 in the regulation of T cell activation in vitro. Methods 90 LN patients, 3 acute kidney injury patients and 20 healthy donors were referred. Disease activity was assessed by SLEDAI scores. The expression of B7-H4 on kidney biopsies from patients with LN and acute kidney injury was measured using immunohistochemistry. In vitro, B7-H4 antigen on cultured HK-2 cells with or without stimulation by inflammatory factors was detected by flow cytometry. After co-cultured with HK-2 and purified CD4+T cells labeled with CFSE for 72 hours, T cell proliferation was detected by flow cytometry. The soluble B7-H4 in sera of LN patients and healthy donors were analyzed using ELISA. Results B7-H4 antigen expressed on tubular epithelium, the percentage of B7-H4 positive expression renal tubules from LN patients (45±16) % was lower than acute kidney injury patients (86±11) % (P<0.05). In vitro, the expression of B7-H4 on HK-2 cells was elevated upon stimulation by inflammatory factors, mixed lymphocyte reactions revealed that HK-2-related B7-H4 inhibits proliferation of co-cultured T cells. The soluble B7-H4 in serum of LN patients (61.45±29.38ng/ml) was not significantly lower than healthy controls (70.57±27.24ng/ml), but stronger association of serum soluble B7-H4 with serum creatinine levels was observed in LN patients (r=0.353, p=0.005). In addition, the mean concentration of soluble B7-H4 level in high activity group (74.40±31.95 ng/ml) was significantly higher than those in moderate group (51.89±21.79 ng/ml) (p=0.017) Conclusions B7-H4 molecules may play a role in the progress of LN, a clear understanding of its functional roles may further elucidate the pathogenesis of this disease. Disclosure of Interest None Declared

Unbalanced expression of aryl hydrocarbon receptor in peripheral blood CCR6+CD4+ and CD4+CD25+T cells of rheumatoid arthritis ☆

OBJECTIVE The goal of this study was to analyze the role of aryl hydrocarbon receptor in peripheral blood CCR6+CD4+ and CD4+CD25+T cells of patients with rheumatoid arthritis. METHODS Flow cytometry was applied to determine the proportion of AhR positive cells in CCR6+CD4+T, CD4+CD25+T and peripheral blood peripheral mononuclear cells from each subject. AhR mRNA and CYP1A1 mRNA relative expression levels were tested by real-time PCR. RESULTS The percentage of AhR positive cells in peripheral blood mononuclear cells was higher in RA group than that in healthy cases [(35.23±10.71)% vs. (18.83±7.32)%, p<0.01]. The expression levels of AhR and CYP1A1 were both increased in patients with RA while compared to controls [(3.71±1.63) vs. (2.00±1.27), p=0.002; (2.62±2.08) vs. (0.62±0.29), p<0.01, respectively]. In RA patients, the percentage of AhR positive cells in CD4+CD25+T cells was significantly lower than that from controls [17.90 (6.10±80.10)% vs. (52.49±19.18)%, p<0.01]; In healthy controls, the percentage of AhR positive cells in CD4+CD25+T cells was significantly higher than that in CCR6+CD4+T cells, and was also significantly higher than that in PBMCs [(52.49±19.18)% vs. (23.18±5.62)% vs. (18.06±7.80)%, X2=24.03, p<0.01]; in RA patients, the percentage of AhR positive cells in CCR6+CD4+T cells was significantly increased than that in CD4+CD25+T cells and PBMCs [(46.02±14.68)% vs. 17.90 (6.10±80.10)% vs. (34.22±10.33)%, X2=38.29, p<0.01]; Nevertheless, no statistically significant relationship was found between clinical data and AhR positive cells in CCR6+CD4+T and CD4+CD25+T cells. CONCLUSION AhR may participate in the pathological progress of RA by controlling the differentiation of Th17 and Treg cells in peripheral blood.

Aberrant GITR expression on different T cell subsets and the regulation by glucocorticoid in systemic lupus erythematosus.

The dysfunction of T regulatory cells is important for the pathogenesis of systemic lupus erythematosus (SLE). Glucocorticoid‐induced tumor necrosis factor receptor family‐related protein (GITR) is expressed at low levels on resting responder T lymphocytes (Tresps) and is up‐regulated on T regulatory cells (Tregs) and activated T cells, diminishing suppressive activity of Tregs and/or leading to resistance to suppression of Tregs by activated effector T cells. We aimed to explore whether SLE patients had an aberrant expression of GITR on Tregs and responder T cells (Tresps) and the regulation by glucocorticoids.

FRI0255 Injection of cd40 dna vaccine ameliorates the autoimmune pathology of non-obese diabetic mice with sjogren’s syndrome

Background In the patients with primary Sjögren’s syndrome (pSS), overexpression of CD40 was reported. The increased CD40 expression contributes to enhance CD40-CD40L interaction and promotes the inflammatory response in various ways. Objectives To investigate whether CD40 DNA vaccine could inhibit the immune response and slow the disease progression of SS in non-obese diabetic (NOD) mice. Methods Female 8-week-old NOD mice were randomly divided into 3 groups. CD40 DNA vaccine group received pTaget CD40 DNA vaccine at a weekly dose of 50 ug for 4 weeks. Vector and NS group were administered an equivalent amount of empty vector or NS. Serum anti-CD40 antibody was measured by ELISA. Lymphocytes infiltration in the salivary glands was monitored by focus score (FS) calculation. Salivary CD40 was stained by immunohistochemistry. Splenic lymphocyte phenotypes were analysed by flow cytometry. CD40, TNF-α and IL-6 levels in the salivary glands were detected by PCR. Serum ANA was monitored by immunoflurescene. Results 1) CD40 DNA vaccination induced anti-CD40 antibody response We found the positive rate on anti-CD40 antibody in vaccine group was 80% at week 6% and 100% at week 10, which was significantly increased compared with that in nonvaccinated ones.(p<0.05 and p<0.01, respectively) 2) Expression of CD40 decreased in salivary glands in vaccine group At week 10, CD40 expression on ductal epithelial and endothelial cells in NOD mice of vaccine group was significantly decreased positive staining. CD40 mRNA expression level showed a significantly reduction compared to vector group (0.51±0.31 vs. 1.56±0.53, p<0.05). 3) Down-regulation of lymphocytes infiltration in the salivary glands of mice in vaccine group At week 10, infiltration of lymphocytes was inhibited in treated group while increased in control group (F=5.275, P<0.05). FS was significantly decreased in vaccine group as compared to NS group (2.00±1.73 vs. 11.33±5.51, P<0.05). Average weight of wet salivary gland and the ratio of average salivary gland weight to body weight of NOD mice in vaccine group were significantly lower than that in control groups (p<0.05 and p<0.05, respectively). 4) CD40 DNA vaccine reduced the expression of TNF-α and IL-6 in the salivary glands In vaccine group, the expression level of TNF-α mRNA in salivary glands were declined significantly as compared to baseline (0.41±0.25 vs. 0.98±0.16, p<0.05) and IL-6 mRNA expression was down-regulated compared with control groups at week 10 (p<0.05; p<0.01, respectively). 5) Disturbances in spleen DC and plasma cell subpopulations At week 6, the total numbers of CD11c+DC decreased as compared with two control groups (p<0.05 and p<0.05, respectively). CD11c+DC and CD19+CD138+plasma cells were significantly reduced compared to basal level (p<0.01 and p<0.05, respectively). 6) Level of ANA reduced in the vaccine group At week 10, the expression of ANA in HEp-2 cells is strong positive (++++) in both control groups, but only positive (+) in vaccine group. Conclusions These findings indicate that CD40 DNA vaccine can downregulate the expression of proinflammatory cytokines of TNF-α and IL-6, decrease the percentage of DCs and plasma cells, ameliorate the pathologic change in NOD mice with SS, and thus inhibit the autoimmune inflammation. Disclosure of Interest None declared

The association between ankylosing spondylitis and the risk of any, hip, or vertebral fracture: A meta-analysis

Background: Ankylosing spondylitis (AS) is an inflammatory rheumatic disease and strongly associated with an increased risk of fractures. A great proportion of patients with AS are suffering from sustaining fractures and the aim of this study is to evaluate and quantify the association between the site of the fracture and AS by performing a meta-analysis. Methods: A systematic literature search was performed on Medline database from 1966 to August 15, 2016 and Embase database from 1980 to August 15, 2016. Studies were evaluated by 2 independent reviewers and quantitative estimates regarding the association between ankylosing spondylitis and the risk of any, hip, or vertebral fracture were presented. After the heterogeneity of selected studies was assessed by using Cochran I2 statistics, the random effect model was used to combine effect size. Publication bias was measured by Egger and Beggs regression tests. Results: A total of 6 articles were involved in our study. The results of meta-analysis revealed that AS was strongly associated with the risk of vertebral fracture (odds ratio [OR] = 4.25, 95% confidence interval [CI] = 1.07–7.42) and was not significantly associated with the risk of any fracture (OR=2.00, 95%CI = 0.94–3.06) or hip fracture (OR=1.28, 95%CI =0.16–2.40). Conclusion: In the present study, a general knowledge of the association between AS and the risk of 3 kinds of fractures were presented, which could improve the ways of prevention of fracture in the patients with AS.

Genetic association of aromatic hydrocarbon receptor and its repressor gene polymorphisms with risk of rheumatoid arthritis in Han Chinese populations

Abstract The goal of this study was to evaluate the potential relationship among polymorphisms of aromatic hydrocarbon receptor, aromatic hydrocarbon receptor repressor, and rheumatoid arthritis (RA) susceptibility as well as the association among the polymorphisms of aromatic hydrocarbon receptor, aromatic hydrocarbon receptor repressor, and their expression. We performed a hospital-based, case–control study of 400 patients with RA and 726 healthy controls in Han Chinese populations. Two single-nucleotide polymorphisms were selected for genotyping including aromatic hydrocarbon receptor (rs2066853) and aromatic hydrocarbon receptor repressor (rs2292596). To single-nucleotide polymorphism rs2292596, a statistically significantly increased risk of RA was found to be associated with the G allele of rs2292596; the odds ratio was 2.170 (95% confidence interval: 1.820–2.587). Unfortunately, no significant differences exhibited in the allelic and the genotype frequencies of rs2066853 between 2 groups. We failed to find any association between rs2066853, rs2292596 genotypes and their expression of patients, respectively. No statistical relationship was found between aromatic hydrocarbon receptor, aromatic hydrocarbon receptor repressor at messenger Ribonucleic acid levels and clinical data, either. This study demonstrated that the polymorphisms of rs2292596 was significant with genetic susceptibility to RA patients; furthermore, it suggests the G allele of rs2292596 might be associated with a dangerous effect on RA in Han Chinese populations.