Soluble HLA Class I Antigens in Patients with Type I Diabetes and Their Family Members

• Published in: Human immunology 1997-07, Vol.55 (2), p.176-183
• Main Authors: Adamashvili, Irena, McVie, Robert, Gelder, Frank, Gautreaux, Michael, Jaramillo, John, Roggero, Tony, McDonald, John
• Format: Article
• Language: English
• Subjects: Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Female; Genetic Variation; Histocompatibility Antigens Class I - blood; Humans; Male
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/S0198-8859(97)00096-7

Our objective was to study a possible contribution of MHC genes to S-HLA-I secretion in patients with Type I diabetes. Quantitatively, we used a highly sensitive enzyme-linked immunoassay to measure S-HLA-I in the serum of a total of 39 patients with Type I diabetes, as well as 36 kinships of 12 diabetic patients and 82 normal individuals with known HLA-phenotypes. S-HLA-I levels were abnormally elevated in patients or their non-diabetic relatives compared to normal controls ( p < 0.0009). No complete HLA-haplotype had been identified to be correlated with high or low S-HLA-I secretion. Only the HLA-A23 or A24 (splits of HLA-A9) positive individuals sera were found to contain high S-HLA-I concentrations in all populations studied. The difference in S-HLA-I levels of HLA-A24 patients ( n = 4) or their HLA-A24 positive non-diabetic relatives ( n = 10) to the group of HLA-A24 normal controls ( n = 15) was statistically highly significant ( p < 0.0005 and p < 0.0009, respectively). The results suggests that HLA-A24 may confer additional independent risk for the disease expression in male children but not in female siblings. Nevertheless, the data implies that the patients or their non-diabetic relatives carrying the HLA-A24 have increased risk of developing ICA associated with high S-HLA-I levels compared to HLA-A24 negative probands or their kinships with low levels of S-HLA-I. This effect occurred irrespective to other diabetes related HLA-DR alleles. In summary, the results show a pronounced genetic heterogeneity of Type I diabetes with MHC control of the expression of S-HLA-I and possible involvement of hormonal factors that might potentiate a specific synthesis of S-HLA-I. The findings have implications for identifying individuals with a possible risk for developing the disease.