Major histocompatibility complex haplotypes and complement C4 alleles in systemic lupus erythematosus. Results of a multicenter study.

Abstract

In a multicenter study more than 300 central European systemic lupus erythematosus (SLE) patients were examined for HLA-B, HLA-DR, and complement C4 phenotypes. For 174 SLE patients MHC haplotypes were determined by family segregation analysis, and for 155 patients C4 gene deletions were determined by TaqI restriction fragment length polymorphism. Two haplotypes, B8-C4AQO-C4B1-DR3 and B7-C4A3-C4B1-DR2, were identified as risk factors for SLE. These findings were confirmed by applying the haplotype frequency difference (HFD) method, which uses nontransmitted haplotypes from the family study as internal controls. Furthermore, only HLA-DR2, but not DR3, B7, or B8, was significantly increased in SLE patients independently of the two risk haplotypes. C4A gene deletions, but not silent C4AQO alleles, were increased in SLE patients and neither C4BQO alleles nor C4B gene deletions were increased. The observed frequencies of homozygosity and heterozygosity for the two haplotypes and the frequencies of homozygotes for C4AQO and C4A deletions did not differ from the expected values, indicating that the risk for SLE is conveyed by single allele effects. In conclusion, there are two MHC-linked susceptibility factors for Caucasian SLE patients carried by the haplotypes B7-DR2 and B8-DR3. The results argue against C4QO alleles being the decisive factors increasing susceptibility to SLE. (J. Clin. Invest. 1992Invest. . 90:1346Invest. -1351

Genetic studies of systemic lupus erythematosus in Asia: where are we now?

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Hla type as a predictor of mixed connective tissue disease differentiation ten‐year clinical and immunogenetic followup of 46 patients

“…However, Hartung et a1 concluded from their study of central European SLE patients that the C4A-null allele is not the decisive factor in increasing susceptibility (34). The association between SSc and the MHC antigens is variable and less clear.…”

The genetics of systemic lupus erythematosus: putting the pieces together

“…61 The C4A null allele is in linkage disequilibrium with HLA-DR3. 62 However, C4A allelic associations with SLE have been noted in some populations without observing an association with HLA-DR3, thereby providing evidence that C4 may have an effect that is independent of HLA. 60,61,[63][64][65] The most frequent homozygous complement deficiency in humans is that of C2.…”