Why are autoimmune rheumatic diseases on the rise? Role of sex and gender among many players: a narrative review

Leonardo Punzi, Marie-Christophe Boissier, Johanna Sigaux, Elodie Rivière
J Sex Gender Specif Med 2024, 10(2): online ahead of print

Abstract. Several epidemiological studies have demonstrated that autoimmune diseases (AIDs) affect about 3-5% of the Western population, with a prevalence that continues to progressively increase, especially among women. Since rheumatological AIDs are among the most common nonorgan- specific AIDs, careful observation of their characteristics may contribute to a better understanding of the possible origin and development of main AIDs. However, we could learn much about the origins of diseases over time. A unique opportunity is provided by rheumatoid arthritis, the most frequent non-organ specific AID, which, according to most historians, was first described in 1800. Consequently, before this date, cases of other AIDs were only rarely reported. Thus, a hypothesis is that AIDs result from relatively recent factors. In this review, we focus on the mosaic of autoimmunity, presenting main aspects that are directly or indirectly involved in the remarkable increase of AIDs within a multifactorial context where genetic, epigenetic, hormonal, and environmental factors act in concert. To categorize these aspects and evaluate potential interactions, we present the ‘exposome’ paradigm. This paradigm allows the inclusion of main environmental factors as potential causative factors for AIDs, particularly in subjects with a genetic predisposition, especially in women.
Keywords. Autoimmunity, epidemiology, sex ratio, genetic, environment.