Showing papers by "Richard S. Spielman published in 1987"

HLA-DQw3.2 allele of the DR4 haplotype is associated with insulin-dependent diabetes; correlation between DQ beta restriction fragments and DQ beta chain variation.

Abstract: The pathophysiology of type I insulin-dependent diabetes (IDDM) is largely unknown, but an autoimmune origin of the disease has been suggested (Bottazzo et al. 1983). Population studies indicate that HLA antigens, especially the class II products, DR3 and DR4, are implicated in the susceptibility to the disease (Rubinstein et al. 1977, Svejgaard et al. 1983). However, because of linkage disequilibrium, it is unclear whether the HLA-DR antigens themselves or the products of other genes closely linked to HLA-DR, such as DP or DQ, are responsible for the disease susceptibility. Furthermore, DR and DQ molecules associated with the DR4 haplotype are heterogeneous (Groner et al. 1983, Holbeck et al. 1985, Bontrop et al. 1986). Therefore, we have used two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and Southern blotting to analyze the DQe alleles found among DR4-positive controls and IDDM patients. After establishing the correspondence of proteins to restriction fragment length polymorphisms (RFLPs), we studied a large number of DR4-positive controls and diabetics to determine the frequency of these polymorphic fragments in the two populations. We are thus able to examine polymorphic variation at the protein and DNA levels simultaneously, and to consider the possible significance of the DQ region for susceptibility to IDDM. • A panel of 12 DR4-positive cell lines has been generated by Epstein-Barr virus transformation of cells from IDDM patients and has been used for the present study. DQ¢ chains of the DR4 haplotype in DR3/4 heterozygotes were identified by using conditions tailored to exclude the DQ~ chain associated with the DR3 haplotype