title: Null alleles of the fourth component of complement and HLA haplotypes in familial systemic lupus erythematosus.
abstract: Eight families (121 individuals) with two or more members affected with systemic lupus erythematosus (SLE) were analyzed for histocompatibility antigens (HLA-A, B, C, DR, MT, and MB) and complement antigens (C4A, C4B, and BF). These data were correlated with serological markers (antinuclear antibodies, single- and double-stranded anti-DNA, anti-SM, anti-nRNP, anti-Ro [SS-A], anti-La [SS-B], and biological false-positive tests for syphilis and clinical features. Fifteen members had SLE, and 19 had other immune diseases (subacute cutaneous lupus erythematosus, discoid lupus erythematosus, hypothyroidism, insulin-dependent diabetes mellitus, primary Sjogren's syndrome, immune thrombocytopenic purpura, rheumatoid arthritis, and multiple sclerosis). Twenty-three healthy relatives (seroreactors) had significant titers of circulating antibodies, as did 2 of 17 spouses. There was an increased frequency of null C4 alleles in those individuals with SLE (60%) and healthy relatives (50%) as compared with spouses (24%). Multivariate analysis showed a significant association between SLE and female sex (P =.006), whereas there was no significant association revealed between female sex and other immune diseases. Patients with SLE also had a higher frequency of either C4A or C4B null alleles (P = .01) than those with immune diseases. The C4A homozygous null phenotype was more common in SLE patients than in seroreactors (P = .02). There was a higher frequency of HLA-DR2 and DR3 in individuals with SLE than in those with immune disease (P = .08), seroreactors (P = .02) and normal relatives (P = .002). One totally C4-deficient patient with SLE was identified. These families demonstrate an important association between SLE and the C4 null allele and the HLA-DR2 and DR3. These risk factors, however, cannot account for the development of disease in all individuals.
mesh_terms: D000328:Adult; D000483:Alleles; D003181:Complement C4 / Q000172:deficiency / Q000235:genetics*; D015934:Complement C4a; D015935:Complement C4b; D005260:Female; D006680:HLA Antigens / Q000235:genetics*; D015802:HLA-DR2 Antigen; D015803:HLA-DR3 Antigen; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012737:Sex Factors
chemical_list: D003181:Complement C4; D006680:HLA Antigens; D015802:HLA-DR2 Antigen; D015803:HLA-DR3 Antigen; D000949:Histocompatibility Antigens Class II; D015934:Complement C4a; D015935:Complement C4b