HLA-DR2-associated Dw subtypes correlate with RFLP clusters: most DR2 IDDM patients belong to one of these clusters.

Two variants of the serologically defined HLA-DR2 specificity have been reported: DR2 long and DR2 short. Distinct HLA-DR2-associated Dw subtypes have been described at the cellular level. In the Israeli population, DR2 individuals may be grouped into three clusters: DR2/Dw2, DR2/Dw12, and DR2/Dw"AZH". A new approach for the study of the polymorphism of HLA class II genes is to investigate restriction endonuclease fragments obtained from genomic DNA with specific class II cDNA probes. Previous analysis of DQ beta restriction endonuclease fragments subdivided the DR2 haplotypes into two subsets: a DQR1-positive subset and a DQR2.6-positive subset. These two subsets behave in the population as alleles that split HLA DQw1. In the present study, we have analyzed class II DQ alpha, DQ beta, and DR beta restriction fragment length polymorphism (RFLP) in HLA-DR2/Dw-typed healthy, unrelated Israeli individuals, as well as in 11 French HLA-DR2 insulin-dependent diabetes mellitus (IDDM) patients and 11 French DR-matched controls. Three DQ beta allelic clusters (DQR2.6, DQR1, and DQR12) were observed among the DR2 haplotypes and clearly correlated with Dw2, Dw"AZH", and Dw12, respectively. The vast majority of the DR2 IDDM patients (9 out of 11) fit into the DQR1 cluster which correlates with Dw"AZH", while only two patients (2 out of 11) belong to the DQR2.6 cluster (Dw2-like). In contrast, among 11 DR-matched healthy controls, 9 belonged to the DQR2.6 cluster and only 2 belonged to the DQR1 cluster. These studies establish the correlation between the DR2-associated Dw subtypes with specific RFLPs, and indicate that the frequency of the DQR1 subset which correlates with Dw"AZH" is increased in DR2 IDDM patients.