Class I Major Histocompatibility Complex (MHC) antigens are prominently expressed on the cell membranes of most nucleated cells; however, soluble form(S-HLA-I) has been described in serum or plasma, and may play a role in immunomodulation or autoimmune disease pathogenesis. To analyze the possible genetic relationship between S-HLA-I levels with MHC alleles in Type I diabetes, we studied the expression of S-HLA-I in the serum of 12 Caucasian patients with Type I diabetes, their 36 unaffected family members and 82 Caucasian individuals with known HLA phenotypes using a solid phase ELISA assay. Serum HLA-I concentrations were significantly higher in patients with Type I diabetes (mean=483 ng/ml) or their blood relatives (mean=424 ng/ml), compared to those values observed in normal controls (mean=241 ng/ml). There was no significant difference in S-HLA-I secretion in terms of the duration of diabetes; however, the stage of “honeymoom” periods were remarkedly longer in those patients who had the high S-HLA-I secretor status(n = 5, mean=812 ng/ml) and shorter in those diabetic patients who showed low S-HLA-I secretion (n = 7, mean=247 ng/ml).
The genetic analysis revealed that high S-HLA-I levels are regulated at least in part by hereditary factors and there is an association between augmented release or production of S-HLA-I and HLA-A24 allotype in families with autoimmune diabetes.
