CHARACTERIZATION OF TYPE-I COMPLEMENT C2-DEFICIENCY MHC HAPLOTYPES - STRONG CONSERVATION OF THE COMPLOTYPE HLA-B-REGION AND ABSENCE OF DISEASE ASSOCIATION DUE TO LINKED CLASS-II GENES/

Fourteen individuals with complete C2 deficiency from 11 families and 3 heterozygous C2-deficient individuals from two families were investi gated. In all the 24 independent C2-deficient haplotypes, the comploty pe S042 was present and the majority (21/24) was [HLA-B18,S042,DR2]. A ll carried the type I C2 deficiency C2 pseudogene with its characteris tic 28 bp deletion. All but two haplotypes had 10 AC/GT repeats in the TNFalpha microsatellite polymorphism and all but one of the haplotype s were identical at or near HLA-B as assessed by RFLP using BstEII dig estion and two genomic probes, R5A and M20A, located 100 and 38 kb cen tromeric to HLA-B, respectively. The exceptional haplotype was HLA-B40 with four AC/GT repeats at TNF-alpha. Three of the haplotypes were no t DR2 based on generic and sequence-specific oligonucleotide typing. A nother four haplotypes showed different DO-variants detected by RFLP a nalysis using Bg/II and Mspl digestion. Thus, the [HLA-B18,S042,DR2] h aplotype appears to be more fixed in the region between the complement genes and the HLA-B locus (96%) than in the region between the comple ment genes and DR (88%) and DO loci (71 %). Of the 14 individuals stud ied, six had SLE or SLE-like syndromes and six had a history of severe infections although two were apparently healthy. Three of the six SLE patients and two individuals with repeated infections were homozygous for [HLA-B18,S042,DR2] and also homozygous for DQB10602 and the comm on DO variant. Thus, MHC class II genes linked to the C2 pseudogene do not appear to determine different clinical consequences of C2 deficie ncy.