BackgroundInterleukin-17 plays important role in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to examine the associations between polymorphisms in the IL17A and IL17F genes and RA.MethodsWe examined 422 RA patients and 337 subjects as a control group. Single nucleotide polymorphism (SNP) in the IL17A (rs2275913) and IL17F (rs763780, rs11465553, rs2397084) genes were genotyped using TaqMan genotyping assays from Life Technologies Genomic.ResultsThere were no significant differences in distribution of IL17A and IL17F genotypes and alleles between RA patients and control group. There were no significant associations between IL17A and IL17F genotypes and age of disease diagnosis rheumatoid factor, erosive disease as well as extra-articular manifestations.ConclusionsThe results of this study suggest, that IL17A and IL17F gene polymorphism are not the important factors associated with susceptibility and some clinical parameters of RA in a Polish population.

Background The intestinal barrier plays an important role in the defense against infections, and nutritional, endocrine, and immune functions. The gut microbiota playing an important role in development of the gastrointestinal tract can impact intestinal permeability and immunity during early life, but data concerning this problem are scarce. Methods We analyzed the microbiota in fecal samples (101 samples in total) collected longitudinally over 24 months from 21 newborns to investigate whether the markers of small intestinal paracellular permeability (zonulin) and immune system development (calprotectin) are linked to the gut microbiota. The results were validated using data from an independent cohort that included the calprotectin and gut microbiota in children during the first year of life. Results Zonulin levels tended to increase for up to 6 months after childbirth and stabilize thereafter remaining at a high level while calprotectin concentration was high after childbirth and began to decline from 6 months of life. The gut microbiota composition and the related metabolic potentials changed during the first 2 years of life and were correlated with zonulin and calprotectin levels. Faecal calprotectin correlated inversely with alpha diversity (Shannon index, r = − 0.30, FDR P (Q) = 0.039). It also correlated with seven taxa; i.a. negatively with Ruminococcaceae (r = − 0.34, Q = 0.046), and Clostridiales (r = − 0.34, Q = 0.048) and positively with Staphylococcus (r = 0.38, Q = 0.023) and Staphylococcaceae (r = 0.35, Q = 0.04), whereas zonulin correlated with 19 taxa; i.a. with Bacillales (r = − 0.52, Q = 0.0004), Clostridiales (r = 0.48, Q = 0.001) and the Ruminococcus (torques group) (r = 0.40, Q = 0.026). When time intervals were considered only changes in abundance of the Ruminococcus (torques group) were associated with changes in calprotectin (β = 2.94, SE = 0.8, Q = 0.015). The dynamics of stool calprotectin was negatively associated with changes in two MetaCyc pathways: pyruvate fermentation to butanoate (β = − 4.54, SE = 1.08, Q = 0.028) and Clostridium acetobutylicum fermentation (β = − 4.48, SE = 1.16, Q = 0.026). Conclusions The small intestinal paracellular permeability, immune system-related markers and gut microbiota change dynamically during the first 2 years of life. The Ruminococcus (torques group) seems to be especially involved in controlling paracellular permeability. Staphylococcus, Staphylococcaceae, Ruminococcaceae, and Clostridiales, may be potential biomarkers of the immune system. Despite observed correlations their clear causation and health consequences were not proven. Mechanistic studies are required. Graphic abstract

BackgroundRheumatoid arthritis (RA) is one of the chronic autoimmune diseases, with genetic and environmental predisposition, and synovial angiogenesis is considered to be a notable stage in its pathogenesis. Angiogenesis or vascular proliferation has been suggested to be a pivotal mechanism involved in both inflammation/immune activation and joint invasion and destruction. RA may be considered an “angiogenic disease” because it is associated with active tissue neovascularization. Vascular endothelial growth factor (VEGF) promotes vascular permeability, regulates angiogenesis, endothelial cell proliferation and migration, chemotaxis, and capillary hyper permeability and therefore is involved in the development of inflammation. VEGF is the most potent proangiogenic molecule promoting the angiogenic phenotype of RA and is upregulated in RA.ObjectivesThe aim of the study was to identify functional VEGF variants and their possible association with VEGF expression, susceptibility to and severity of RA.Methods581 RA patients and of 341 healthy individuals were examined for -1154 A/G, -2578 A/C VEGF gene polymorphisms by PCR-RFLP method and for -634 G/C VEGF gene polymorphisms by TaqMan SNP genotyping assay. Serum VEGF levels in RA patients and controls were measured by ELISA.ResultsThe -1154 A/G VEGF gene polymorphism under the codominant, recessive (AA+AG vs. GG) and dominant (AA vs. AG+GG) models were associated with RA (p = 0.0009; p = 0.004; p = 0.017, respectively). VEGF -2578 A/C revealed differences in the case-control distribution in codominant, recessive, dominant and overdominant models (all p<0.0001). Furthermore, the -634 G/C VEGF gene SNP was not correlated with susceptibility to RA in Polish population. The genotype-phenotype analysis showed significant association between the VEGF -1154 A/G and -634 G/C and mean value of the hemoglobin (all p = 0.05), additionally they relevated that the number of women with the polymorphic allele -2578 C was lower than the number of women with wild type allele -2578A (p = 0.006). Serum VEGF levels were significantly higher in RA patients than in control groups (both p = 0,0001).ConclusionPresent findings indicated that VEGF genetic polymorphism as well as VEGF protein levels may be associated with the susceptibility to RA in the Polish population.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint destruction caused by infiltrating leukocytes including T cells. An important role in T cell co-stimulation is played by the CD28, as a stimulatory signal transducer and the inhibitory CTLA-4. CCL5 is produced by circulating T cells and plays an active role in the chemotactic activity of T cells in RA. The aim of this study was to examine the associations between polymorphisms within CD28, CTLA-4, and CCL5 genes and RA. We examined 422 patients (340 female, 82 male, mean age 57.5 ± 12.5 years) with rheumatoid arthritis and 338 healthy subjects (261 female, 77 male). Disease activity was determined on the basis of DAS28 score. The patients with DAS28 of ≤2.5 were classified as subjects in remission of disease symptoms; the patients who had DAS28 of >2.5 were classified as subjects with active form of RA. There were no statistically significant differences in the distribution of studied genotypes and alleles between RA patients and the control group. A statistically significant difference was observed in the distribution of CTLA4 exon 1 +49A>G rs231775 genotypes between patients with DAS28 ≤ 2.5 and DAS28 > 2.5 where the increased frequency of AA genotype among patients with DAS28 > 2.5 was revealed (OR 1.55; 95% CI 1.01-2.38). The results of our study suggest no significant association between CD28 rs1980422, CCL5 rs2107538, CTLA-4 exon 1 +49A>G rs231775 and rs3087243 gene polymorphisms and RA in the Polish population. Our results indicate a possible association between CTLA-4 exon 1 +49A>G rs231775 gene polymorphism and RA activity.

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