Autoimmunity and Klinefelter's syndrome: when men have two X chromosomes.
Similar to other autoimmune diseases, systemic lupus erythematosus (SLE) predominately affects women. Recent reports demonstrate excess Klinefelter's among men with SLE and a possible under-representation of Turner's syndrome among women with SLE as well as a case report of a 46,XX boy with SLE. These data suggest that risk of SLE is related to a gene dose effect for the X chromosome. Such an effect could be mediated by abnormal inactivation of genes on the X chromosome as has been demonstrated for CD40L, or by genetic polymorphism as has been demonstrated for Xq28. On the other hand, a gene dose effect could also be mediated by a gene without an SLE-associated polymorphism in that a gene that avoids X inactivation will have a higher level of expression in persons with two X chromosomes.
Sawalha
Amr H
AH
Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Harley
John B
JB
Scofield
R Hal
RH
D000782:Aneuploidy; D000818:Animals; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology; D041321:Chromosomes, Human, X; D005260:Female; D018628:Gene Dosage / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007713:Klinefelter Syndrome / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D008297:Male; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012729:Sex Chromosome Aberrations; D012737:Sex Factors
D023201:CD40 Ligand