Although the existing paradox with respect to the immunomodulating role of steroid hormones in RA remain unresolved, it seems to be reasonable to hypothesize that the presence of ESR2 polymorphisms that correlate either with ESR2 mRNA expression levels may influence on the risk of developing bone erosions in RA likely through the modulation of ESR2-dependent tolerogenic immune responses. The gene discussed is ESR2; the disease is rheumatoid arthritis.