Etiology and Risk Factors for Rheumatoid Arthritis: A State-of-the-Art Review

Abstract

Rheumatoid arthritis (RA) is the most common systemic inflammatory rheumatic disease. It is associated with significant burden at the patient and societal level. Extensive efforts have been devoted to identifying a potential cause for the development of RA. Epidemiological studies have thoroughly investigated the association of several factors with the risk and course of RA. Although a precise etiology remains elusive, the current understanding is that RA is a multifactorial disease, wherein complex interactions between host and environmental factors determine the overall risk of disease susceptibility, persistence and severity. Risk factors related to the host that have been associated with RA development may be divided into genetic; epigenetic; hormonal, reproductive and neuroendocrine; and comorbid host factors. In turn, environmental risk factors include smoking and other airborne exposures; microbiota and infectious agents; diet; and socioeconomic factors. In the present narrative review, aimed at clinicians and researchers in the field of RA, we provide a state-of-the-art overview of the current knowledge on this topic, focusing on recent progresses that have improved our comprehension of disease risk and development.

A Review of Metabolomic Profiling in Rheumatoid Arthritis: Bringing New Insights in Disease Pathogenesis, Treatment and Comorbidities

“…Metabolic changes presented by RA patients can be linked to pathogenic mechanisms and may represent a possible way to understand environmental and genetic factors related to inflammatory diseases [ 10 ]. Since metabolism is important to the regulation of immune cells development, immunometabolism studies bring new insights about pathogenicity mechanisms, drug response, management of comorbidities and disease follow-up [ 5 , 11 , 12 , 13 ].…”

RNA Editing–Associated Post-Transcriptional Gene Regulation in Rheumatoid Arthritis

“…RA risk factors include genetic and epigenetic factors, exposure to certain chemicals, and lifestyle-related factors such as diet and smoking. 35 Our results strongly indicate that RNA editing could provide an additional level of gene regulation in RA. While RNA editing may be unlikely as the primary factor behind RA aetiology, it could contribute to disease progression and severity of the disease.…”

Low-Density Lipoprotein Cholesterol and the Risk of Rheumatoid Arthritis: A Prospective Study in a Chinese Cohort

“…We do not expect that this could substantially impact our results, as the prevalence of lipid-lowering medication use in China is low [ 26 , 27 ]. It was also not possible to account for other important RA risk factors not measured in this study, including family history and exposure to silica dust [ 28 ]. Furthermore, while cigarette smoking has been reported to be associated with an elevated risk of RA, [ 28 ] we did not observe a significant effect of smoking on RA risk in this cohort.…”

“…It was also not possible to account for other important RA risk factors not measured in this study, including family history and exposure to silica dust [ 28 ]. Furthermore, while cigarette smoking has been reported to be associated with an elevated risk of RA, [ 28 ] we did not observe a significant effect of smoking on RA risk in this cohort. This may be due to the low incidence of RA in this Chinese population (lack of statistical power), or to the limitation that our measure of smoking did not account for the duration or amount of cigarettes smoked on average.…”