Systemic lupus erythematosus (SLE) is ten times more common in women than in men. The question of why women are predisposed to SLE has been asked for several decades. Instead, the PI has asked why some men acquire SLE. The answer that a few men have SLE because they are 47.XXY may led to an answer of the broader question as to why women get SLE. Previous data concerning SLE and Klinefelter's syndrome consist of only case reports or small case series. Turner's syndrome has been reported in association with SLE only twice. Preliminary data developed by the PI demonstrate that Klinefelter's syndrome (47.XXY) is found in excess among SLE-affected men SLE with 5 of 207 also having Klinefelter's syndrome. None of 1000 women with SLE so far studied have Turner's syndrome (45.XO). Microsatellite typing of families with 2 or more SLE patients indicate that a susceptibility gene for SLE lies on chromosome X at q28. Together, these data imply a gene dose effect for the X chromosome and SLE susceptibility gene (or genes) found thereon. The hypothesis that a gene dose effect exists will be tested. Based on this hypothesis, the PI predicts that 47.XXY men and 47.XXX women are found in excess among patients with SLE and 45.XO women are not, and that a susceptibility gene for SLE is present on the X chromosome. Furthermore, the PI hypothesizes that SLE among men with Klinefelter's syndrome will not be severe disease characteristic of SLE men but will instead be similar to SLE found in women. Therefore, the specific aims of this proposal will test these hypotheses. First, a large cohort of men with SLE will be collected from the Center for Medicare Services database, which the PI and his colleagues have used with success in the past. The rate of 45.XO and 47.XXX among women with SLE will be determined. The clinical manifestations of SLE will be compared between 47.XXY men and 46.XY men as well as 46.XX women. In the third and fourth specific aim the statistically powerful and established genetic linkage on the X chromosome will be pursued with the hypothesis that a gene dose effect is present for the susceptibility gene. Systemic lupus affects women much more commonly than men such that up to 1 in 250 Black American women are affected. This proposal will determine whether the presence of two X chromosomes is a risk factor for women and men with Klinefelter's syndrome (47,XXY).
| Liu, Ke; Kurien, Biji T; Zimmerman, Sarah L et al. (2016) X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased Prevalence of 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome. Arthritis Rheumatol 68:1290-1300 |
| Harris, Valerie M; Sharma, Rohan; Cavett, Joshua et al. (2016) Klinefelter's syndrome (47,XXY) is in excess among men with Sjögren's syndrome. Clin Immunol 168:25-29 |
| Aggarwal, Rachna; Sestak, Andrea L; Chakravarty, Eliza F et al. (2013) Excess female siblings and male fetal loss in families with systemic lupus erythematosus. J Rheumatol 40:430-4 |
| Kurien, Biji T; D'Sousa, Anil; Bruner, Benjamin F et al. (2013) Prolidase deficiency breaks tolerance to lupus-associated antigens. Int J Rheum Dis 16:674-80 |
| Dillon, Skyler P; Kurien, Biji T; Li, Shibo et al. (2012) Sex chromosome aneuploidies among men with systemic lupus erythematosus. J Autoimmun 38:J129-34 |
| James, Judith A; Robertson, Julie M (2012) Lupus and Epstein-Barr. Curr Opin Rheumatol 24:383-8 |
| Rasmussen, Astrid; Sevier, Sydney; Kelly, Jennifer A et al. (2011) The lupus family registry and repository. Rheumatology (Oxford) 50:47-59 |
| Aggarwal, R; Sestak, A L; D'Souza, A et al. (2010) Complete complement deficiency in a large cohort of familial systemic lupus erythematosus. Lupus 19:52-7 |
| Aggarwal, Rachna; Namjou, Bahram; Li, Shibo et al. (2010) Male-only systemic lupus. J Rheumatol 37:1480-7 |
| Dillon, Skyler P; D'Souza, Anil; Kurien, Biji T et al. (2009) Systemic lupus erythematosus and C1q: A quantitative ELISA for determining C1q levels in serum. Biotechnol J 4:1210-4 |
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