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Originally published online as doi:10.2353/ajpath.2008.071008 on August 7, 2008

Published online before print August 7, 2008
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(American Journal of Pathology. 2008;173:600-609.)
© 2008 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2008.071008

Review

Sex Differences in Autoimmune Disease from a Pathological Perspective

DeLisa Fairweather*{dagger}, Sylvia Frisancho-Kiss* and Noel R. Rose{dagger}{ddagger}

From the Departments of Environmental Health Sciences* and Pathology,{dagger} and the W. Harry Feinstone Department of Molecular Microbiology and Immunology,{ddagger} the Johns Hopkins Medical Institutions, Baltimore, Maryland

Abstract

Autoimmune diseases affect ~8% of the population, 78% of whom are women. The reason for the high prevalence in women is unclear. Women are known to respond to infection, vaccination, and trauma with increased antibody production and a more T helper (Th)2-predominant immune response, whereas a Th1 response and inflammation are usually more severe in men. This review discusses the distribution of autoimmune diseases based on sex and age, showing that autoimmune diseases progress from an acute pathology associated with an inflammatory immune response to a chronic pathology associated with fibrosis in both sexes. Autoimmune diseases that are more prevalent in males usually manifest clinically before age 50 and are characterized by acute inflammation, the appearance of autoantibodies, and a proinflammatory Th1 immune response. In contrast, female-predominant autoimmune diseases that manifest during the acute phase, such as Graves’ disease and systemic lupus erythematosus, are diseases with a known antibody-mediated pathology. Autoimmune diseases with an increased incidence in females that appear clinically past age 50 are associated with a chronic, fibrotic Th2-mediated pathology. Th17 responses increase neutrophil inflammation and chronic fibrosis. This distinction between acute and chronic pathology has primarily been overlooked, but greatly impacts our understanding of sex differences in autoimmune disease.






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Copyright © 2008 by the American Society for Investigative Pathology.