Causal risk and protective factors in rheumatoid arthritis: A genetic update

Abstract

The characterization of risk and protective factors in complex diseases such as rheumatoid arthritis (RA) has evolved from epidemiological studies, which test association, to the use of Mendelian randomization approaches, which test direct relationships. Indeed, direct associations with the mucosal origin of RA are retrieved with periodontal disease ( Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans predominantly), interstitial lung involvement, tobacco smoking and air pollutants. Next, factors directly associated with an acquired immune response include genetic factors (HLA DRB1, PTPN22), capacity to produce anti-modified protein antibodies (AMPA), and relatives with a history of autoimmune diseases. Finally, factors can be also classified according to their direct capacity to interfere with the IL-6/CRP/sIL-IL6R proinflammatory pathway as risk factor (body fat, cardiometabolic factors, type 2 diabetes, depressive syndrome) or either as protective factors by controlling of sIL-6R levels (higher education level, and intelligence). Although some co-founders have been characterized (e.g. vitamin D, physical activity, cancer) the direct association with sex-discrepancy, pregnancy, and infections among other factors remains to be better explored.

Helicobacter pylori and its association with autoimmune diseases: systemic lupus erythematosus, rheumatoid arthritis and Sjögren syndrome

“…Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovial membrane inflammation damage to articular cartilage and juxta-articular bone [ 67 ]. Microorganisms such as Porphyromonas gingivalis , gut microbiota, and the herpes simplex virus are associated with the etiopathogenesis of RA [ 68 ]; in addition, there are antecedents that H. pylori eradication worsens RA activity [ 69 ]. However, the association between H. pylori infection and RA is not well-understood [ 35 , 70 ].…”

Novel insights into the complex interplay of immune dysregulation and inflammatory biomarkers in preeclampsia and fetal growth restriction: A two-step Mendelian randomization analysis

“…Compared to previous studies [ [56] , [57] , [58] ], this study has both strengths and limitations. The strengths include a thorough examination of the relationships between various autoimmune diseases and PE, specifically PE with FGR.…”

Restoring the Balance between Pro-Inflammatory and Anti-Inflammatory Cytokines in the Treatment of Rheumatoid Arthritis: New Insights from Animal Models

“…Lungs are constantly exposed to insults due to infections, injury, and inhalants, dust, silica, asbestos, and especially tobacco smoke [ 1 , 2 , 3 ]. In addition, bacterial infections in the oropharynx, leading to gingivitis or periodontal disease, are considered a possible key early factor (see reviews) [ 1 , 4 , 5 , 6 , 7 ]. The inflammatory responses that drive RA usually originate with autoimmune responses against normal, modified or immuno-mimetics of self-proteins that are often found within skeletal joints.…”