Sex ratio and rheumatic disease: excerpts from an Institute of Medicine report

Abstract

Some autoimmune diseases have high female/male (F/M) ratios. Definitions and classi”cations of autoimmune diseases differ, as do the F/M ratios themselves. The sex ratio of lupus is the single most prominent, little explored clinical fact that may lead to understanding of how lupus and other autoimmune diseases occur. The objective of this study was to evaluate evidence for causes of high F/M ratios of autoimmune and non-immunologic diseases. This was done by a literature review. Some thyroid, rheumatic and hepatic diseases consistently have high F/M ratios; other autoimmune diseases have low ratios. Because F/M ratios reflect disease incidence, not disease severity, an intrinsic biologic cause for the F/M ratios (such as estrogen) would be likely to act through a threshold or permissive mechanism rather than through quantitative immunomodulation. Sex differences related to environmental exposure, X-inactivation, imprinting, X or Y chromosome genes and intrauterine influences are other possible explanations for sex differences of incidence. The epidemiology of the sex discrepant autoimmune diseases, young, female, suggests that an explanation for sex discrepancy lies in differential exposure, vulnerable periods or thresholds, rather than in quantitative aspects of immunomodulation.