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This study aimed to investigate the role of TSPAN32, a member of the tetraspanin family, in rheumatoid arthritis (RA). The objective was to assess the expression levels of TSPAN32 in experimental RA models and in RA patient immune cells, exploring its potential as a regulatory factor in RA pathogenesis. The study employed adjuvant‐induced arthritis in rats and collagen‐induced arthritis (CIA) in mice as experimental models. Ex vivo analyses included evaluating TSPAN32 expression in immune cells at different stages of the disease. In silico data analysis involved examining transcriptomic datasets from drug‐naïve and treated RA patients to correlate TSPAN32 expression with clinical parameters. TSPAN32 overexpression experiments in splenocytes from CIA mice aimed to demonstrate its functional impact on antigen‐specific immune responses. The animal models revealed a significant downregulation of TSPAN32, particularly in synovial‐infiltrating T cells. Also, TSPAN32 overexpression inhibited pro‐inflammatory cytokine production in splenocytes. In RA patients, TSPAN32 was consistently downregulated in circulating and synovial‐infiltrating T cells, as well as in CD8+ T cells, B cells and NK cells. Drug treatment did not significantly alter TSPAN32 levels. Negative correlations were observed between TSPAN32 expression and inflammatory markers (CRP, ESR) and clinical scores (SDAI) in RA patients. This study suggests that reduced TSPAN32 expression characterizes pathogenic T‐cell populations in RA, highlighting its potential as biomarker for inflammation and disease activity. TSPAN32 may play a crucial role in shaping adaptive immune responses in RA, opening avenues for novel therapeutic strategies targeting this tetraspanin family member. [ABSTRACT FROM AUTHOR]

Background: The increased expression of B cell‐activating factor (BAFF) has been linked to autoantibody production in autoimmune diseases (ADs). The aim of this study was to investigate the association among TNFSF13B gene (OMIM: 603969) single nucleotide polymorphisms (SNPs), TNFSF13B mRNA, and soluble BAFF (sBAFF) expression in patients with rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS). The diagnostic value of sBAFF also was evaluated by the area under the curve (AUC) of receiver operating characteristic or receptor (ROC) curves. Methods: Genotypes of the TNFSF13B rs9514827 (−2841 T > C), rs1041569 (−2701 A > T) and rs9514828 (−871 C > T) SNPs were determined by PCR‐RFLP assay. TNFSF13B mRNA and sBAFF expression were performed by RT‐qPCR and ELISA, respectively. The study included 320 RA patients, 101 pSS patients, and 309 healthy subjects (HS). Results: The rs9514828 T allele and the TAT haplotype were associated with an increased risk to develop RA. In both ADs, the TNFSF13B mRNA levels were increased in comparison with HS. The rs9514828 (−871 C > T) polymorphism was associated with increased gene expression in RA patients. Also, sBAFF levels were higher in both ADs, however pSS patients showed the highest sBAFF levels. sBAFF showed higher diagnostic performance for pSS with an AUC of 0.968, with a similar accuracy of anti‐SSA/Ro antibody diagnosis (AUC = 0.974). Conclusions: Our findings demonstrate that the TNFSF13B rs9514828 (−871 C > T) polymorphism is a risk factor for RA in the western Mexican population. sBAFF levels may be a potential diagnosis biomarker in pSS. [ABSTRACT FROM AUTHOR]

Peptidyl arginine deiminase IV (PADI4) enzyme catalyzes the citrullination of proteins, which are recognized by anti-cyclic citrullinated peptide antibodies (anti-CCP) in rheumatoid arthritis (RA) patients. Here, we determined the association between PADI4 gene polymorphisms and haplotypes with RA susceptibility and clinical characteristics in a western Mexican population. The relationship of PADI4 polymorphisms with anti-CCP and PADI4 mRNA expression was also evaluated. PADI4_89, PADI4_90 and PADI4_92 polymorphisms were individually associated with RA susceptibility. The GTG haplotype was significantly associated with: RA susceptibility; disease onset at ≤40 years and anti-CCP antibodies. PADI4 expression was three fold higher in RA patients carrying the susceptibility haplotype (GTG) than in non-susceptibility haplotype carriers (ACC). In conclusion, polymorphisms and functional haplotype (GTG) in PADI4 are associated with RA susceptibility as well as anti-CCP antibodies in a Mexican population. This supports the role of PADI4 early in RA pathogenesis by promoting the generation of citrullinated autoantigens. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The PTPN22 gene encodes lymphoid tyrosine phosphatase LYP, a potent negative regulator of T cell activation. Polymorphic variants of this gene have previously been associated with various autoimmune disorders. The +1858C/T single-nucleotide polymorphism (SNP) (rs2476601), in the exon 14 of the PTPN22 gene has been associated with susceptibility to RA in several population. Objective: The aim of this work was to investigate whether the +1858C/T of the PTPN22 gene is associated with susceptibility to RA in Western Mexico population. Methods: A total of 309 unrelated RA patients, classified according to American College of Rheumatology (ACR) 1987 criteria, as well as 347 controls residents from Western Mexico were recruited for this study. The DNA samples were genotyped for +1858C/T PTPN22 gene SNP using the PCR-RFLP technique. Antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). Results: The frequency of +1858T risk allele was significantly increased in patients with RA compared with controls (p =0.001, OR=2.83, 95%CI=1.50–5.32). To confirm this results we established a comparison between subjects carrying of CT+TT genotypes versus those carrying CC genotype, between both groups (p =0.004, OR=2.65, 95%CI=1.33–5.36). Nevertheless, we not observed association of the +1858C/T PTPN22 gene SNP with clinical activity and functional disability in RA patients. Likewise, the +1858T variant in RA patients seropositive for anti-CCP antibodies, increased the risk for RA (p =0.008, OR=2.5, 95%CI=1.3–5.0) when we compared with controls; however, in the group of seronegative patients, no was found significant difference (p =0.1, OR=2.5, 95%CI=0.9–7.2). Conclusions: Our results support the association of the +1858T risk allele of the +1858C/T PTPN22 polymorphism with susceptibility to RA and confirm that, in combination with anti-CCP antibodies, this SNP influence the autoimmune processes towards a development of RA in Mexican population. [Copyright &y& Elsevier]

To investigate the association of sICAM-1 and sVCAM-1 with ICAM1 721G>A and VCAM1 1238G>C polymorphisms and rheumatoid arthritis (RA) clinical activity, sixty RA patients and 60 healthy non-related subjects (HS) matched for age and sex were recruited. Soluble adhesion molecules were determined by ELISA technique. Rheumatoid factor (RF), C reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were measured by routine methods. Disability and clinical activity was measured with Spanish-HAQ-DI and DAS28 scores, respectively. The ICAM1 and VCAM1 polymorphism were identified using the PCR-RFLP procedure. Inter-group comparison showed increased levels of sICAM-1 and sVCAM-1 in RA patients (284 and 481 ng/mL) versus HS (132 and 280 ng/mL); in the RA group, significant correlations between sVCAM-1 and RF (r = 0.402), ESR (r = 0.426), Spanish-HAQ-DI (r = 0.276), and DAS28 (r = 0.342) were found, whereas sICAM-1 only correlated with RF (r = 0.445). In RA patients, a significant association with the 721A allele of ICAM1 polymorphism (p = 0.04), was found. In addition, the allele impact (G/A+A/A) of this polymorphism was confirmed, (p = 0.038, OR = 2.3, C.I. 1.1–5.0). sVCAM-1 and sICAM-1 serum levels reflected the clinical status in RA, independently of the ICAM1 and VCAM1 polymorphism. However, the ICAM1 721A allele could be a genetic marker to RA susceptibility. [ABSTRACT FROM AUTHOR]