Increased autoimmunity in men with Klinefelter’s syndrome: Sex chromosome dosage effect (P3309)

Abstract

Abstract Autoimmune diseases are more common in women than in men. Studies in animal models suggest a role of sex chromosome genotype in modulating autoimmune susceptibility. Here, we begin to translate these murine findings onto humans. Our hypothesis is that X chromosome dosage, rather than the female sex itself, imparts susceptibility to autoimmune diseases. Our results show that levels of IgG anti-chromatin and anti-nucleosome autoantibodies were significantly higher in men with sex chromosome aneuploidy (47,XXY) compared to 46,XY men. XXY men, however, did not have non-specific B cell hyper-reactivity, as the levels of anti-thyroid peroxidase antibody that is associated with autoimmune thyroid disease were similar between the two groups. A preliminary analysis of completed questionnaire revealed an increase in autoimmune and inflammatory conditions when compared with known population prevalence of these diseases. Analysis of immune cell phenotype and responses conducted thus far showed a significant reduction in the frequency of natural killer T cells in 47,XXY men as compared to 46,XY men. These data suggest a role of X chromosome dosage in inducing autoimmunity in humans. Since animals and humans with autoimmune diseases have reduced numbers and/or functions of natural killer T cells, our observation of reduced natural killer T cells in 47,XXY men may be related to increased autoimmunity in these men.