Rheumatoid arthritis (RA) is an autoimmune disease with an unclear pathogenic mechanism. However, it has been proven that the key underlying risk factor is a genetic predisposition. Association studies of the HLA-DRB1 gene clearly indicate its importance in RA morbidity. This review presents the current state of knowledge on the impact of HLA-DRB1 gene, functioning both as a component of the patient’s genome and as an environmental risk factor. The impact of known HLA-DRB1 risk variants on the specific structure of the polymorphic HLA-DR molecule, and epitope binding affinity, is presented. The issues of the potential influence of HLA-DRB1 on the occurrence of non-articular disease manifestations and response to treatment are also discussed. A deeper understanding of the role of the HLA-DRB1 gene is essential to explore the complex nature of RA, which is a result of multiple contributing factors, including genetic, epigenetic and environmental factors. It also creates new opportunities to develop modern and personalized forms of therapy.

Objectives: The aim of our study was to determine whether there is a correlation between transcription factors expression and Th17/Treg ratio, cytokine profile in the RA phenotype as well as to identify transcription factors that could be a potential biomarker for RA.Methods: The study was conducted on 45 patients with RA, 27 patients with OA and 46 healthy controls (HCs). Th17 and Treg frequency was determined by flow cytometry (15 patients with RA/OA and 15 subjects of HC). Gene expression was estimated by qPCR, and the serum cytokine levels were determined by ELISA.Results: The percentage of Treg (CD4+CD25highCD127-) cells in RA patients was lower than in OA patients or HCs. Proportions of Th17 (CD4+CCR6+CXCR3-) cells were higher in RA and OA in comparison to HCs. STAT5 showed a very high expression in the blood of RA patients compared to healthy subjects. The expression of STAT5 and HELIOS was not detected in Th17 cells. A positive correlation between SMAD3 and STAT3 in RA patients was observed. Negative correlations between HIF-1A and SMAD2 in RA Treg cells and DAS-28 score were observed. The range of serum of IL-17 and IL-21 were higher in RA patients than in OA patients. Concentrations of serum IL-2 and IFN-γ were higher in RA and OA patients than in healthy subjects. Based on the ROC analysis, the diagnostic potential of the combination of HIF1A, SMAD3 and STAT3, was determined at AUC 0.95 for distinguishing RA patients from HCs. For distinguishing RA patients from OA patients the diagnostic potential of the combination of SMAD2, SMAD3, SMAD4 and STAT3, was determined at AUC 0.95.Conclusion: Based on our study, we conclude that SMAD3 and STAT3 could be potential diagnostic biomarkers for RA.

Tumor necrosis factor-alpha (TNF-α) is a multifunctional Th1 cytokine and one of the most important inflammatory cytokines. In pregnancy, TNF-α influences hormone synthesis, placental architecture, and embryonic development. It was also shown that increased levels of TNF-α are associated with pregnancy loss and preeclampsia. Increased TNF-α levels in complicated pregnancy draw attention to trophoblast biology, especially migratory activity, syncytialisation, and endocrine function. Additionally, elevated TNF-α levels may affect the maternal-fetal relationship by altering the secretory profile of placental immunomodulatory factors, which in turn affects maternal immune cells. There is growing evidence that metabolic/pro-inflammatory cytokines can program early placental functions and growth in the first trimester of pregnancy. Furthermore, early pregnancy placenta has a direct impact on fetal development and maternal immune system diseases that release inflammatory (e.g., TNF-α) and immunomodulatory factors, such as chronic inflammatory rheumatic, gastroenterological, or dermatological diseases, and may result in an abnormal release of cytokines and chemokines in syncytiotrophoblasts. Pregnancy poses a challenge in the treatment of chronic disease in patients who plan to have children. The activity of the disease, the impact of pregnancy on the course of the disease, and the safety of pharmacotherapy, including anti-rheumatic agents, in pregnancy should be considered.

Interleukin‐17F (IL‐17F) is a novel proinflammatory cytokine. IL‐17F gene is an excellent candidate for chronic inflammatory disease. We investigated the association between rheumatoid arthritis (RA) and His161Arg (7488A/G; rs763780) and Glu126Gly (7383A/G; rs2397084) polymorphism of IL‐17F gene. The gene polymorphisms in 220 Polish patients with RA and 106 healthy subjects were amplified by polymerase chain reaction with restriction endonuclease mapping. Overall, the polymorphisms of the IL‐17F gene were not correlated with susceptibility to RA in Polish population. However, the IL‐17F His161Arg variant was associated with parameters of disease activity, such as number of tender joints, HAQ score or DAS‐28‐CRP. Moreover, our findings have shown that Glu126Gly IL‐17F gene polymorphism may be correlated with longer disease duration in patients with RA. Our results for the first time showed the relationship between IL‐17F gene polymorphisms and severity of RA.