ASSOCIATION OF HLA-A24 WITH COMPLETE BETA-CELL DESTRUCTION IN IDDM

作者：NAKANISHI K^*; KOBAYASHI T; MURASE T; NAKATSUJI T; INOKO H; TSUJI K; KOSAKA K

来源：Diabetes, 1993, 42(7): 1086-1093.

DOI：10.2337/diabetes.42.7.1086

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 DO 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. Even when the patients were stratified according to the duration of diabetes, HLA-A24 was more common in those with early complete loss of beta-cell duration of diabetes < 1 yr) (P = 0.035) and was less common in those with residual beta-cell function despite a long duration of diabetes (> 10 yr) (P = 0.001). The correlation between HLA-A24 positivity and complete beta-cell loss also was confirmed in younger-onset (< 30 yr old) and elder-onset (greater-than-or-equal-to 30 yr old) groups. The C-peptide immunoreactivity response in patients with HLA-A24 (0.09 +/- 0.02 nM, mean +/- SE, n = 74) was significantly lower than that in patients without HLA-A24 (0.19 +/- 0.03 nM, n = 37, P < 5.0 x 10(-5)). Further typing of HLA-A24 by one-dimensional isoelectric focusing gel electrophoresis revealed that the isoelectric point of HLA-A24 was identical in charge in 17 of 18 patients and 7 normal control subjects (isoeletric point 6.32, HLA-A24.1). We conclude that a specific HLA class I antigen, HLA-A24, promotes pancreatic beta-cell destruction in IDDM patients with other disease-susceptible HLA antigens.

• 出版日期1993-7
• 单位河北医科大学