A DECREASE IN THE ESTIMATED FREQUENCY OF THE EXTENDED HLA HAPLOTYPE B18 CF130 DR3 DQW2 IS COMMON TO NON-INSULIN-DEPENDENT DIABETES, JUVENILE RHEUMATOID-ARTHRITIS, AND BERGERS-DISEASE

Extended HLA haplotypes frequencies were estimated from the HLA, C2, B f and C4 phenotypes of 74 patients with non-insulin-dependent diabetes (NIDD), 92 with juvenile rheumatoid arthritis (JRA), 44 with Berger's disease (BD), 83 with insulin-dependent diabetes (IDD), and 140 healt hy controls. The extended HLA haplotype B18 CF130 DR3 DQw2, which is c ommon (around 10% phenotype frequency) in healthy Spaniards and in oth er populations of paleo-North African origin, was found to be signific antly less frequent in NIDD, JRA and BD, whereas its frequency was nor mal in IDD (although DR3 DQw2 haplotypes were increased in the latter disease). These data support the existence of a common HLA-linked path ogeneic mechanism in NIDD, JRA and BD, and point to a genetic differen ce between IDD and NIDD at the HLA level. This effect is readily detec table in our population because the uncommon BfF1 allele marks that ha plotype instead of the more common BfS, which marks B8 CS01 DR3 DQw2 i n other Caucasians. Our results support the hypothesis of strong selec tive pressures operating at the HLA level to preserve extended HLA hap lotypes with advantageous gene sets from dilution by crossing-over. Im balanced incomplete haplotypes may give rise to inappropriate T-cell r epertoire selection in the thymus and/or antigen handling in the perip hery, and be partly responsible for the pathogenesis of certain HLA-li nked diseases (i.e. NIDD, JRA, and BD).