Aim: The activation of NLRP3 inflammasome leads to the stimulation of cytokines and is significantly involved in the pathogenesis and progression of autoimmune diseases. The purpose of this study is to examine the associations of NLRP3 gene polymorphisms with rheumatoid arthritis (RA) and primary Sjogren’s syndrome (SS) patients. Methods: A total of 239 patients with RA, 285 patients with primary SS, and 170 healthy controls were enrolled. Genomic DNA was extracted from peripheral blood mononuclear cells, and gene polymorphisms were genotyped through the TaqMan assay. Antinuclear antibody (ANA), anti-Ro, and anti-CCP antibodies were detected using immunofluorescence immunoassay. Results: The T allele of rs4612666 CT elevated the susceptibility to RA disease. The RF titer during diagnosis of RA was significantly high in RA patients with the A allele of rs12079994 G/A polymorphism. The titer of anti-CCP during diagnosis of RA was high in the absence of the C allele of rs10754558 C/G polymorphisms in RA patients. Antinuclear antibody and anti-CCP were positively associated with the A allele of rs12079994 G/A polymorphism in primary SS. The C allele of rs4612666 C/T was negatively associated with ANA in primary SS. Conclusions: The results have shown that NLRP3 gene polymorphisms may play a role in the pathogenesis of RA and primary SS.

Background: GADD45 genes are stress sensors in response to cellular stress response, activated signal pathways leading to the stimulation of inflammatory cytokines. This study is to examine the associations of GADD45a and GADD45b genes with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients. Methods: 230 patients of RA, 140 patients of SLE, and 191 healthy controls were enrolled. Genomic DNA was extracted from peripheral blood mononuclear cells and gene polymorphisms were genotyped by TaqMan assay. RNA expression was quantitated with real-time polymerase chain reaction. Results: The RNA expression of the GADD45b gene was significantly lower in RA patients than the control cases (p = 0.03). The odds ratio of GADD45a genotype -589 CC (rs581000) was significantly low (OR = 0.36, 95% CI, 0.15–0.87) in DR4-negative RA patients. The odds ratio of GADD45b genotype -712CT (rs3795024) in DR4-negative RA patients was 0.41 (95% CI, 0.18–0.95). In clinical manifestation, the odds ratio of GADD45b -712CT genotype with anti-RNP antibody was 4.14 (95% CI, 1.10–15.63) in SLE patients. GADD45a genotype -589GG+GC was associated with rheumatoid factor (RF) in SLE patients. Conclusions: Genotypes GADD45a -589CC and GADD45b -712CT were shown to be less susceptible to RA and related to the disease state in SLE patients.

(1) Background: It is widely accepted that aberrant methylation patterns contribute to the development of systemic lupus erythematosus (SLE). Ten–eleven translocation (TET) methylcytosine dioxygenase is an essential enzyme of which there are three members, TET1, 2, and 3, involved in hydroxymethylation, a newly uncovered mechanism of active DNA methylation. The epigenomes of gene transcription are regulated by 5-hydroxymethylcytocine (5-hmC) and TETs, leading to dysregulation of the immune system in SLE. The purpose of this study was to investigate the global hydroxymethylation status in SLE peripheral blood mononuclear cells (PBMCs) and to explore the role of TETs in changing the patterns of methylation. (2) Methods: We collected PBMCs from 101 SLE patients and 100 healthy donors. TaqMan real-time polymerase chain-reaction assay was performed for the detection of 5-methylcytosine (5-mC), 5-hmC, and TET2 mRNA expression and single-nucleotide polymorphism genotyping. The methylation rates in different CpG sites of TET2 promoters were examined using next-generation sequencing-based deep bisulfite sequencing. Putative transcription factors were investigated using the UCSC Genome Browser on the Human Dec. 2013 (GRCh38/hg38) Assembly. (3) Results: 5-mC and 5-hmC were both decreased in SLE. The mRNA expression level of TET2 was notably high and found to be correlated with the levels of immunologic biomarkers that are indicative of SLE disease activity. The analysis of methylation rates in the TET2 promoter revealed that SLE patients had significantly higher and lower rates of methylation in TET2 105146072-154 and TET2 105146218-331, respectively. (4) Conclusions: TET2 may play an important role in 5-mC/5-hmC dynamics in the PBMCs of SLE patients. The epigenetic modification of TET2 promoters could contribute to the pathogenesis of SLE and the intensity of the immunologic reaction.

To date, there has been no studies to evaluate the incidence of Crohn’s disease in systemic sclerosis patients. The goals of this study were to evaluate the incidence of Crohn’s disease and its relationship with sex and age in patients with systemic sclerosis. We enrolled patients with systemic sclerosis and controls from Taiwan’s Registry of Catastrophic Illness Database and National Health Insurance Research Database. Every systemic sclerosis patient was matched to at most three controls by sex, age, month and year of initial diagnosis of systemic sclerosis. The standardized incidence ratio (SIR) of Crohn’s disease in systemic sclerosis patients, and 95 % confidence interval (95 % CI) were calculated. Cox hazard regression was used to calculate the hazard ratio (HR). The study enrolled 2,829 patients with systemic sclerosis and 8,257 controls. Male and female patients with systemic sclerosis both had lower rates of incident Crohn’s disease (SIR: 0.18, 95 % CI = 0.05–0.62; SIR: 0.10, 95 % CI = 0.05–0.21, respectively). The risk of incident Crohn’s disease in systemic sclerosis was still lower than in controls when we stratified the patients according to their ages. In Cox hazard regression, the hazard rates of Crohn’s disease were lower in systemic sclerosis patients after adjusting for genders and ages (HR: 0.12, 95 % CI = 0.06–0.21, p < 0.001). Systemic sclerosis is associated with decreased incidence of, irrespective of sex and age of the patients.

Aim: To investigate the clinical response to adalimumab (ADA) in patients with active radiographic axial spondyloarthritis (r‐axSpA) in Taiwan. Methods: In this real‐world study, patients with r‐axSpA, starting ADA therapy, were enrolled and followed up every 12 weeks for 48 weeks. Outcome parameters were the proportion of patients with an improvement of 50% in Bath ankylosing spondylitis disease activity index (BASDAI50), inactive disease (ID, < 1.3), and low disease activity (LDA, < 2.1) per ankylosing spondylitis disease activity score–C‐reactive protein (ASDAS‐CRP) and ASDAS‐erythrocyte sedimentation rate (ASDAS‐ESR), and change in peripheral and extra‐musculoskeletal manifestations. Determinants of BASDAI50 response to ADA were examined. Treatment‐emergent adverse events (TEAEs) were recorded. Results: Of 88 enrolled patients, 86 were analyzed, and 82 completed the study with all patients receiving 40 mg ADA fortnightly. Patients achieving BASDAI50 increased from 79.1% to 80.5% from weeks 12 to 48. At week 48, ASDAS‐CRP and ‐ESR, ID, and LDA were improved from baseline in 60.8%, 74.7%, 42.1%, and 68.4% of patients, respectively. A decrease in enthesitis, peripheral arthritis, dactylitis, and uveitis was noted. Younger age, presence of uveitis, and use of conventional synthetic disease‐modifying antirheumatic drugs were the determinants of treatment response. At least one TEAE was reported in 22.7%, serious AEs in 2.3% of patients, and no deaths. The most common TEAEs were upper respiratory tract infection (5.7%) and cough (3.4%). Conclusions: This real‐world, prospective study in Taiwan involving patients with active r‐axSpA shows that ADA treatment effectively reduced disease activity and improved physical function. No new safety concerns were noted.

Background: Maintaining physical function and preserving spinal flexibility have been challenging in managing ankylosing spondylitis (AS). Most rehabilitation programs, including manual therapy, massage, hydrotherapy, and acupuncture, cannot be performed at home. The effect of transcutaneous electrical nerve stimulation (TENS) was validated in treating AS, but no home TENS system has explored its efficacy to date. Objective: This study aims to evaluate the efficacy of a home TENS system with a novel treatment program for patients with AS. Methods: The modified WeHeal TS-200 TENS and galvanic response system provided home-based TENS treatment for patients with AS. Patients were divided into a 2-month course group and a 1-month course group. After the first treatment course, patients went through a washout period for the same duration of their treatment course. Participants could decide whether to accept the second course of treatment. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Schober test, finger-to-floor flexion test, enthesis score, cytokines, chemokines, inflammatory factors, and immunoglobulins were measured to evaluate its efficacy. The clinical trial protocol (1096607481) received approval from the Ministry of Health and Welfare in Taiwan. Results: A total of 9 patients (5 in a 2-month course group and 4 in a 1-month course group) completed the first treatment course, and 5 patients (4 in a 2-month course group and 1 in a 1-month course group) completed the sequential treatment course. The weighted results showed that patients reported an improving BASFI score (mean difference –0.9, SD 1.7; P=.03) after treatment. Looking into the trajectories, declined BASFI and BASDAI scores were noticed during treatments; this score increased during the washout period. There were improving trends in the Schober test (mean difference 1.9, SD 4.9; P=.11) and finger-to-floor flexion test (mean difference –0.6, SD 9.5; P=.79), but the results were not statistically significant. The response of cytokines, chemokines, inflammatory factors, and immunoglobulins before and after treatment did not show a consistent trend, and all results were not statistically significant (all P>.05). Conclusions: The home TENS device demonstrated a potential role in AS management. It may improve accessibility and adherence for patients with AS and provide remote monitoring for clinicians. Further research can compare the effectiveness of electrotherapy at home or in a medical setting and focus on integrating the home TENS system and exercise program to enhance patients’ physical functions and spinal flexibility.