Genetic studies of human lupus in families.
Systemic lupus erythematosus (SLE) is a complex multigenic disease in which the contributing genetic systems are being rapidly identified. Most of the currently recognized genes have been discovered from case-control association studies, but, increasingly, family linkage studies are being employed to confirm previous genetic associations, to examine their relative contributions, and to identify new susceptibility loci. Most of the loci identified thus far appear to contribute only modest effects on susceptibility overall but rather influence more strongly disease expression and/or severity. MHC class II alleles, for example, seem to show only weak linkage to SLE itself but instead mediate specific T cell driven pathogenic autoantibodies which produce many of the clinical disease features, similar to their effects in many other autoimmune diseases. On the other hand, complete and partial hereditary deficiencies of early complement components are more lupus-specific. Homozygous complement deficiencies, while powerful risk factors, are rare causes of lupus and heterozygous deficiencies exert only modest effects on susceptibility. Other genes, such as low-binding IgG Fc receptor alleles (FcgammaIIa and FcgammaIIIa), appear to promote nephritis by modifying the efficiency of immune complex clearance. A variety of cytokine genes appear also to promote severity, including those for TNFalpha, IL-10, IL1 receptor antagonist, and perhaps others (IL-6, IL-4 and TNFalpha receptor). Family studies and recent genome-wide scans in lupus and other autoimmune diseases support the likelihood that some susceptibility loci, as yet unidentified, predispose to several or many autoimmune diseases. Only thorough the identification and elucidation of function of these many genes is the pathogenic picture of lupus likely to be complete.
Arnett
F C
FC
University of Texas-Houston Health Science Center, USA.
D003165:Complement System Proteins / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D005190:Family; D005803:Genes, Immunoglobulin; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics
D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003165:Complement System Proteins