Sex bias in autoimmunity

Abstract

Purpose of review: To give an overview of recently published articles addressing the mechanisms underlying sex bias in autoimmune disease.

Recent findings: Recent studies investigating the origins of sex bias in autoimmune disease have revealed an extensive and interconnected network of genetic, hormonal, microbial, and environmental influences. Investigation of sex hormones has moved beyond profiling the effects of hormones on activity and prevalence of immune cell types to defining the specific immunity-related genes driving these changes. Deeper examination of the genetic content of the X and Y chromosomes and genetic escapees of X chromosome inactivation has revealed some key drivers of female-biased autoimmunity. Animal studies are offering further insights into the connections among microbiota, particularly that of the gut, and the immune system.

Summary: Sex bias in autoimmune disease is the manifestation of a complex interplay of the sex chromosomes, sex hormones, the microbiota, and additional environmental and sociological factors.

Figure 1.. The sex distribution of the major autoimmune diseases.

The numbers above the bars refer to the total number of disease cases (×1,000,000) in the USA (3). SLE: systemic lupus erythematosus.

Figure 2.. Female sex alone carries a risk of autoimmunity four times greater than any other known genetic risk variant for SLE.

Odds ratio (OR) for female sex was calculated based on prevalence data from the Georgia Lupus Registry from 2002 (6). ORs are shown for allelic associations at SLE susceptibility loci from a genome-wide association replication study (7).