Association of ICOS Expression with Focus Score and Immunoglobulins The ICOS expression related to focus score, immunoglobulin levels, and the presence of Ro/La antibodies as possible risk factors in patients with pSS were evaluated

Association of ICOS Expression with Focus Score and Immunoglobulins The ICOS expression related to focus score, immunoglobulin levels, and the presence of Ro/La antibodies as possible risk factors in patients with pSS were evaluated. 0.015, CI = 0.294C0.884). An increase in mRNA expression in patients was observed (3.7-fold). Furthermore, pSS patients showed an increase in membranal-ICOS expression (mICOS). High expression of mICOS (MFI) was associated with lymphocytic infiltration. Conclusions: The IVS1 + 173 polymorphism is not a genetic marker for the development of pSS, while c.1624 T allele was associated with a low risk. However, elevated mICOS expression in pSS patients with high lymphocytic infiltration was found. ICOS may have an important role in the immunopathogenesis of pSS and should be analyzed in T cell subsets in pSS patients RP-64477 as a possible disease marker. Keywords: ICOS, polymorphism, primary Sj?grens syndrome, autoimmune diseases 1. Introduction Primary Sj?grens syndrome (pSS) is a systemic autoimmune disease characterized by dry eyes and a dry mouth [1], and systemic manifestations, such as general fatigue, fever, and damage to multiple organs [2]. In addition, immunological abnormalities include antinuclear antibodies (ANAs), antibodies directed against Ro or La ribonucleoproteins, and hypergammaglobulinemia [3,4]. In primary Sj?grens syndrome, an imbalanced immune response is usually mediated by T cells in the early stages of disease [5,6,7], which causes cellular infiltrate. In this line, the expression of co-stimulatory proteins is necessary for the proper functioning of the immune system [8]. Experimental evidence has linked co-stimulatory proteins in many inflammatory processes such as infections, cancer, and autoimmunity [9,10,11]. In general, co-stimulatory molecules can be classified as stimulatory or inhibitory, some are even constitutively expressed such as CD28; however, there are others such as ICOS that are inducible, critical to the T cell response. ICOS results in enhanced signals to activate transcription factors such as nuclear factor-B (NF-B), nuclear factor of activated T cells (NFAT), and activator protein 1 (AP1) [12]. In addition, ICOS also directly influences T-helper cell differentiation into T-helper cell type 1 (Th1), Th2, or Th17 subsets [10,12,13], and more recently, ICOS has been directly implicated in the induction of a specific T cell effector subset known as T follicular helper (Tfh) cells [13]. The co-stimulatory receptor ICOS (CD278) is critical for T cell activation and the RP-64477 generation, function, and maintenance of Tfh and extrafollicular T helper cells that help germinal center RP-64477 reaction to produce antibodies [11]. Therefore, are associated with several autoimmune diseases, few studies have investigated the role of ICOS in primary Sj?grens syndrome. Polymorphisms in have been associated with susceptibility to autoimmune diseases such as coeliac disease [16], pemphigus [17], and autoimmune hepatitis type 1 [18]. Furthermore, recent studies demonstrate that ICOS expression was up regulated in SGs but also in peripheral blood mononuclear cells (PBMCs) in pSS. In addition, the expression of ICOS was closely associated with lymphocytic infiltration in SGs and disease activity of pSS patients [19]. Evidence demonstrated that these polymorphisms (IVS1 + 173 T/C and c.1624 C/T) in the gene affect its transcription [20,21]. This occurs by various mechanisms such as RNA-binding proteins that control gene expression post-transcriptionally by recognizing multiple stem-loop structures in their 3-UTRs. By this mechanism, Roquin-regulated mRNAs encode costimulatory receptors such as ICOS, CTLA-4, and Ox40 [22]. In the present study, given the importance of ICOS as a mediator of inflammation, we analyzed polymorphisms of (IVS1 + 173 T/C and c.1624 C/T) in primary Sj?grens syndrome which have not been previously studied in this disease. This study aimed to investigate the possible association between polymorphisms and expression in pSS and the severity of the disease. 2. Methods 2.1. Study Group Primary Sj?grens syndrome patients [(= 134; mean age (range) 55 (29C83); 133 patients were female and 1 was male] who satisfied the criteria of the American College of Rheumatology/European League Against Rheumatism 2016 without any other type Rabbit polyclonal to XRN2.Degradation of mRNA is a critical aspect of gene expression that occurs via the exoribonuclease.Exoribonuclease 2 (XRN2) is the human homologue of the Saccharomyces cerevisiae RAT1, whichfunctions as a nuclear 5′ to 3′ exoribonuclease and is essential for mRNA turnover and cell viability.XRN2 also processes rRNAs and small nucleolar RNAs (snoRNAs) in the nucleus. XRN2 movesalong with RNA polymerase II and gains access to the nascent RNA transcript after theendonucleolytic cleavage at the poly(A) site or at a second cotranscriptional cleavage site (CoTC).CoTC is an autocatalytic RNA structure that undergoes rapid self-cleavage and acts as a precursorto termination by presenting a free RNA 5′ end to be recognized by XRN2. XRN2 then travels in a5′-3′ direction like a guided torpedo and facilitates the dissociation of the RNA polymeraseelongation complex of autoimmune diseases, were enrolled from the Rheumatology Service of the Hospital General de Occidente (Zapopan, Mxico) and Hospital Civil Fray Antonio Alcalde, Guadalajara, Mxico..