Microbial players in autoimmunity: multicentric analysis of the association between <i>Mycoplasma hominis</i> serostatus and rheumatoid arthritis

Resident mucosal pathogens may induce immune tolerance breach, specific autoimmune response, and the development of rheumatoid arthritis (RA) in susceptible individuals. Despite a number of studies linking infections by <i>Mollicutes</i> bacteria to autoimmune disorders' onset and progression, the role of <i>Mycoplasma hominis</i>, a common urogenital mucosa colonizing bacterium, in inducing a specific humoral response in RA has been seldom addressed. This study reports <i>M. hominis</i> seroprevalence in RA patients compared to healthy controls (HC) by testing two separate cohorts sampled in two distinct geographical settings (Italy and Vietnam). The amount of circulating anti-lipid-associated membrane proteins (LAMPs) antibodies was significantly higher in RA patients than HC in both cohorts. Also, a significantly higher seroprevalence of anti-<i>M</i>. <i>hominis</i> antibodies in RA patients compared to HC in both cohorts was observed. Notably, neither ELISA OD values nor positivity of anti-LAMPs were significantly associated with RA-specific variables. Further studies are essential to elucidate the underlying mechanisms by which <i>Mycoplasma</i> species may contribute to the pathogenesis of RA, thereby advancing our understanding of the potential causal links between <i>Mollicutes</i> and autoimmune disorders.IMPORTANCEMycoplasmas may cause persistent asymptomatic mucosal infections and elicit chronic host immune responses. In this study, we evaluated the prevalence of serological response to the sexually transmitted bacterium <i>Mycoplasma hominis</i> in patients with rheumatoid arthritis. We show that sera of patients with rheumatoid arthritis are enriched with antibodies specifically recognizing microbial surface antigens compared with the general population. This suggests that <i>M. hominis</i> genital infection, with its peculiar host immunity subversion mechanisms, might play a role in predisposing to the development and progression of chronic arthritis in susceptible individuals. Thus, the range of microbes with a role as triggers of autoimmune disease (<i>P. gingivalis</i>, A. <i>actinomycetemcomitans</i>, <i>Streptococcus</i> spp., and <i>F. nucleatum</i>, among others) might have a new member in <i>M. hominis</i>. The potential role of the interactions taking place at the host-pathogen interface during persistent <i>M. hominis</i> infections in inducing autoimmunity should be further explored and characterized.