Synchronous decline of serum-soluble HLA class I antigen and beta-cell function in insulin-dependent diabetes mellitus.
Serum-soluble HLA class I molecules (sHLA) have immunomodulatory functions and their serum levels correlate with the HLA class I phenotype. We studied longitudinal changes of serum sHLA levels in insulin-dependent diabetes mellitus (IDDM). A total of 198 serum samples were obtained from 40 IDDM patients before and after IDDM onset. sHLA was assayed by a sandwich ELISA. sHLA levels in IDDM patients at the initiation of insulin therapy (IDDM onset) were markedly reduced compared with those in normal controls (334.2 +/- 26.3 ng/ml vs 492.4 +/- 55.5 ng/ml, mean +/- SEM, P = 0.0038). They fell sharply during 6 months before and after the onset of IDDM. The dynamic profile of sHLA and the time course of beta-cell loss were different between IDDM patients with and without HLA-A24. In those with HLA-A24, sHLA became significantly lower than normal controls with HLA-A24 at IDDM onset. Recovery of their sHLA values occurred at 3 years from IDDM onset. On the other hand, in those without HLA-A24, sHLA levels began to decrease since the onset of IDDM and became significantly lower than normal controls without HLA-A24 at 4 years after the onset. Recovery of sHLA occurred at more than 6 years from the onset. An early (within 18 months), complete loss of beta-cell function occurred in 5 of 13 IDDM patients with HLA-A24 compared with 1 of 14 of those without HLA-A24 (P = 0.077). A late (more than 36 months after the onset of IDDM), complete loss of beta-cell function occurred in 7 of 14 IDDM patients without HLA-A24 but in none of 13 of those with HLA-A24 (P = 0.0058). These results indicate that the decline of sHLA is synchronous with massive beta-cell destruction, and that these events occur during a short period in IDDM patients with HLA-A24, whereas they occur during a relatively long period in those without HLA-A24.
Nakanishi
K
K
Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, Japan.
Kobayashi
T
T
Komatsu
Y
Y
Kogawa
N
N
Hagihara
M
M
Tsuji
K
K
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000276:immunology / Q000503:physiopathology; D005260:Female; D015234:HLA-A Antigens / Q000097:blood*; D059871:HLA-A24 Antigen; D015395:Histocompatibility Antigens Class I / Q000097:blood*; D006801:Humans; D007515:Islets of Langerhans / Q000502:physiology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged
D001323:Autoantibodies; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D015395:Histocompatibility Antigens Class I