New evidence suggesting an X chromosome effect underlies the development and progression of male systemic lupus erythematosus comes from a study of sex chromosome aneuploidy in men with this disease. The description of a number of immunoregulatory mechanisms encoded on the X chromosome support this hypothesis; however, further studies are warranted.
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References
Lu, L., Wallace, D. J., Ishimori, M. L., Scofield, R. H. & Weisman, M. H. Male systemic lupus erythematosus: a review of sex disparities in the disease. Lupus 19, 119–129 (2010).
Dillon, S. P. et al. Sex chromosome aneuploidies among men with systemic lupus erythematosus. J. Autoimmun. 38, J129–J134 (2012).
Scofield, R. H. et al. Klinefelter's syndrome (47,XXY) in male systemic lupus erythematosus patients: support for the notion of a gene-dose effect from the X chromosome. Arthritis Rheum. 8, 2511–2517 (2008).
Chagnon, P. et al. Identification and characterization of an Xp22.33;Yp11.2 translocation causing a triplication of several genes of the pseudoautosomal region 1 in an XX male patient with severe systemic lupus erythematosus. Arthritis Rheum. 54, 1270–1278 (2006).
Hughes, T. et al. Analysis of autosomal genes reveals gene–sex interactions and higher total genetic risk in men with systemic lupus erythematosus. Ann. Rheum. Dis. http://dx.doi.org/10.1136/annrheumdis2011200385.
Sawalha, A. H. et al. Sex-specific differences in the relationship between genetic susceptibility, T cell DNA demethylation and lupus flare severity. J. Autoimmun. 38, J216–J222 (2012).
Lu, Q. et al. Demethylation of CD40LG on the inactive X in T cells from women with lupus. J. Immunol. 179, 6352–6358 (2007).
Sawalha, A. H. et al. Common variants within MECP2 confer risk of systemic lupus erythematosus. PLoS ONE 3, e1727 (2008).
Jacob, C. O. et al. Identification of IRAK1 as a risk gene with critical role in the pathogenesis of systemic lupus erythematosus. Proc. Natl Acad. Sci. USA 106, 6256–6261 (2009).
Shen, N. et al. Sex-specific association of Xlinked Toll-like receptor 7 (TLR7) with male systemic lupus erythematosus. Proc. Natl Acad. Sci. USA 107, 15838–15843 (2010).
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E. Peeva is a stock holder or director of Pfizer and Merck. G. Zandman-Goddard declares no competing interests.
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Zandman-Goddard, G., Peeva, E. Unravelling aetiology in male SLE—the X chromosome dose effect. Nat Rev Rheumatol 8, 310–312 (2012). https://doi.org/10.1038/nrrheum.2012.44
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DOI: https://doi.org/10.1038/nrrheum.2012.44
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