, Volume 40, Issue 1, pp 42-49
Date: 10 Jan 2010

The Unexplained Female Predominance of Systemic Lupus Erythematosus: Clues from Genetic and Cytokine Studies

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Despite recent progress in the understanding of systemic lupus erythematosus (SLE), the striking 9:1 female to male ratio of disease incidence remains largely unexplained. In addition, peak SLE incidence rates occur during the early reproductive years in women. Studies which illuminate potential causes underlying this sex difference and characteristic onset during the reproductive years have the potential to fundamentally advance our understanding of disease pathogenesis in SLE. Similarly, progress in this area will likely inform human reproductive immunology. Studies of sex hormone function in the immune system are of obvious importance; however, it seems likely that many other types of sex-related genetic and immunological differences will contribute to SLE. In this review, we will focus on recent work in sex-related differences in cytokine pathways and genetics of these pathways as they relate to SLE pathogenesis. It seems quite possible that many of these sex-related differences could be important to reproductive fitness, which may explain the conservation of these immune system features and the observed female predominance of SLE.

C. E. Weckerle has no grant support or disclosures to declare. Grant support for and disclosures by T. B. Niewold include NIH K08 AI083790, NIAID Clinical Research Loan Repayment AI071651, Arthritis National Research Foundation Eng Tan Scholar Award, Lupus Research Institute Novel Research Grant, University of Chicago CTSA Core Subsidy Grant, and Collaborative University of Chicago/Northshore University Health System Translational Research Pilot Grant from UL1 RR024999.