Gut microbiota, by influencing multiple metabolic processes in the host, is an important determinant of human health and disease. However, gut dysbiosis associated with metabolic complications show...

Summary: Antibodies against cyclic citrullinated peptides (anti-CCP) are widely used for diagnosis of rheumatoid arthritis (RA). We performed a comparative analysis of antibodies targeting the citrullinating enzyme peptidylarginine deiminase type 4 (anti-PAD4) and mutated citrullinated vimentin (anti-MCV) with anti-CCP autoantibodies in RA patients and examined their relationships with clinical parameters, cytokine profiles and the PADI4 gene. Autoantibodies were examined by enzyme-linked immunosorbent assay (ELISA) in sera of 170 RA patients and 103 controls. Cytokine profiles were measured using a multiplex system. PADI4 polymorphisms (89G > A, 90T > C and 92G > C) were genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Anti-PAD4, anti-MCV and anti-CCP autoantibodies were detected in 24, 61 and 74% of RA patients, respectively. Positive correlations were observed between anti-PAD4 and disease duration; anti-CCP and erythrocyte sedimentation rate (ESR); anti-MCV and ESR and C-reactive protein. Anti-MCV antibodies were associated with high disease activity score 28 (DAS-28) in early RA. Concentrations of T helper type 1 (Th1) [tumour necrosis factor (TNF)-α, interleukin (IL)-12, IL-2, IL-1β], Th2 (IL-4, IL-6, IL-10, IL-13) and Th17 (IL-17) cytokines were higher in RA than in controls. Th2 and, to a lesser extent, Th1-related cytokines, showed positive correlations with anti-MCV and anti-CCP. The GTG haplotype in PADI4 was associated with anti-CCP and anti-MCV, but not anti-PAD4 antibodies. In conclusion, anti-PAD4 antibodies are detected mainly in established RA, which is in contrast to the early detection of antibodies against citrullinated peptide/proteins (ACPAs). Among autoantibodies, anti-MCV appear to perform better as markers of disease activity. Furthermore, anti-CCP and anti-MCV are associated genetically with the citrullinating enzyme PAD4 and are related strongly to Th1 and Th2 cytokines, suggesting a feed-forward loop between cytokines and ACPA production.

Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease that can cause joint damage. Among the environmental risk factors, diet plays an important role because it can aggravate or attenuate inflammation. Selenium (Se) is considered an essential trace element since it is a structural component of antioxidant enzymes; however, its concentration can be affected by diet, drugs and genetic polymorphisms. Studies have reported that RA patients have a deficient diet in some food groups that is associated with parameters of disease activity. Furthermore, it has been shown that there is an alteration in serum Se levels in this population. Although some clinical trials have been conducted in the past to analyze the effect of Se supplementation in RA, no significant results were obtained. Contrastingly, experimental studies that have evaluated the effect of novel Se nanoparticles in RA-induced models have shown promising results on the restoration of antioxidant enzyme levels. In particular, glutathione peroxidase (GPx) is an important selenoprotein that could have a modulating effect on inflammation in RA. Considering that RA patients present an inflammatory and oxidative state, the aim of this review is to give an overview of the current knowledge about the relevance of Se status in RA.