Association of HLA-A24 With Complete β-Cell Destruction in IDDM

Abstract

A sensitive C-peptide immunoreactivity radioimmunoassay demonstrated the presence of subtle, but definite residual beta-cell function in patients with IDDM of long duration. Although HLA antigens are known to influence susceptibility to IDDM, their contribution to the extent of pancreatic beta-cell destruction has not yet been examined extensively. We studied the relationship between residual beta-cell function and HLA class I and class II antigens in 111 unrelated Japanese IDDM patients. Using the sensitive C-peptide immunoreactivity radioimmunoassay, the presence or absence of residual beta-cell function was evaluated by the C-peptide immunoreactivity response to a 100-g oral glucose load. DNA typing for HLA-DQA1 and HLA-DQB1 antigens was performed in addition to serological typing of HLA-A, HLA-B, HLA-C, and HLA-DR antigens. A C-peptide immunoreactivity response > 0.033 nM was regarded as an indication of the presence of residual beta-cell function, not the assay error. Surprisingly, 35 of 37 (94.6%) patients without residual beta-cell function had HLA-A24, whereas only 39 of 74 (52.7%) patients with residual beta-cell function had this antigen (corrected P = 9.795 x 10(-6). Any other HLA antigens, including the DR and DQ loci, showed no difference in the frequency with regard to residual beta-cell function. The duration of diabetes was similar between the groups with and without residual beta-cell function.(ABSTRACT TRUNCATED AT 250 WORDS)