Association of HLA-A24 with complete beta-cell destruction in IDDM.
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)
Nakanishi
K
K
Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, Japan.
Kobayashi
T
T
Murase
T
T
Nakatsuji
T
T
Inoko
H
H
Tsuji
K
K
Kosaka
K
K
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D002096:C-Peptide / Q000097:blood*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D005260:Female; D005951:Glucose Tolerance Test; D015234:HLA-A Antigens / Q000097:blood* / Q000235:genetics*; D059871:HLA-A24 Antigen; D006683:HLA-DQ Antigens / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011863:Radioimmunoassay; D012016:Reference Values
D002096:C-Peptide; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D006683:HLA-DQ Antigens; D009838:Oligodeoxyribonucleotides