Genetic and environmental risk factors for rheumatoid arthritis

Abstract

Multiple genetic and environmental factors have been associated with an increased risk for rheumatoid arthritis (RA). Of these, the strongest associations have been seen with female sex, a family history of RA, the genetic factor the ‘shared epitope’ and with exposure to tobacco smoke. There is also renewed interest in mucosal inflammation and microbial factors as contributors to the development of RA. However, the identification of a ‘preclinical’ period of RA that can be defined as local or systemic autoimmunity as measured by autoantibodies and other biomarkers prior to the development of clinically-apparent synovitis suggests that the risk factors for RA are acting long prior to first clinical evidence of IA. As such, a major challenge to the field will be to investigate the full spectrum of the development of RA, from initiation and propagation of autoimmunity during preclinical RA and transition to clinically-apparent synovitis and classifiable RA, in order to determine which genetic and environmental factors are important at each stage of disease development. Understanding the exact role and timing of action of risk factors for RA is especially important given the advent of prevention trials in RA, and the hope that a full understanding of genetic and environmental factors in RA could lead to effective preventive interventions.

Laboratory diagnostics and pathogenesis of rheumatoid arthritis — the past and the present

“…protein tyrosine phosphatase gene (PTPN22) or signal transducer and activator of transcription 4 (STAT4) [4][5]. The relationship between the presence of anti-CCP antibodies and a shared epitope in RA patients is also described [4,8]. It emerges that in patients with shared epitope, the concentration of anti-CCP significantly depends on environmental factors, i.e.…”

“…The exact mechanism is unknown, but an early preclinical effect of hormones in the development of RA is probable. It is thought that exogenous hormones lead to a decrease in the secretion of endogenous hormones, and thus a decrease in the risk of developing the disease [4]. Furthermore, the contribution of various microbes, including bacteria or www.journals.viamedica.pl/medical_research_journal bacterial antigens, viruses, as well as mucosal inflammation, to the development of RA has been observed [5].…”

“…Many specific genetic loci are also responsible for the increased risk of RA, e.g. protein tyrosine phosphatase gene (PTPN22) or signal transducer and activator of transcription 4 (STAT4) [4][5]. The relationship between the presence of anti-CCP antibodies and a shared epitope in RA patients is also described [4,8].…”

“…This factor is a potential cause of increased antibody synthesis, especially in patients with a genetic predisposition to RA. In addition, tobacco smoke affects the growth of periodontal and lung diseases, which can lead to inflammatory and autoimmune changes initiating the systemic action that is the development of RA [4,7]. Various dietary factors, including high intake of sugar, cheese, red meat, or protein increase the risk of developing RA, while a healthy diet based on low consumption of sugar and animal fats, and rich in fruits and vegetables, reduces the risk of disease [4].…”

“…It has been proven that a positive family history has been associated with an increased risk of RA [1,4]. Due to the three-fold more frequent incidence of the disease in women, the participation of female-specific factors in the pathogenesis of RA is also taken into account.…”