HLA antigens and age at diagnosis of insulin-dependent diabetes mellitus

• Published in: Human immunology 1995-02, Vol.42 (2), p.116-122
• Main Authors: Tait, Brian D., Harrison, Leonard C., Drummond, Bruce P., Stewart, Vicky, Varney, Michael D., Honeyman, Margo C.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age Factors; Child; Child, Preschool; Diabetes Mellitus, Type 1 - diagnosis; Diabetes Mellitus, Type 1 - immunology; Female; HLA-D Antigens - genetics; HLA-DP Antigens - genetics; HLA-DQ Antigens - genetics; HLA-DR Antigens - genetics; Humans; Infant; Male
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/0198-8859(94)00075-2

IDDM results from the immune-mediated destruction of pancreatic islet β cells. Clinicopathologic heterogeneity in IDDM is reflected in part by the wide age range over which the onset of clinical symptoms can occur, after months to years of subclinical “insulitis.” Because MHC genes play a critical role in immune function we studied their possible contribution to IDDM heterogeneity by analyzing HLA profiles of 194 IDDM patients in relation to their age at diagnosis. Restriction of HLA-DR heterogeneity was observed in patients diagnosed before age 21 years. Frequencies of DR3 and DR 3 4 were highest in the ⩽6-year-old age group and thereafter declined with increasing age at diagnosis. In contrast, the frequency of DR4 remained increased up to age 30 years at diagnosis. DR7, normally considered to be a neutral allele, was like DR2 and DR 5, significantly decreased in patients diagnosed before age 21 years. The A30-B18-DR3 haplotype was significantly increased in the ⩽6-year-old age group, A1-B8-DR3 was increased in the ⩾31-year-old group. B62-DR4 was increased only in the > 12-year-old age group. In DR4 patients the frequency of DQ8 was increased across all age groups. A sex difference was observed in those diagnosed at ⩽ 12 years of age, with an excess of females in the DR3 +/DR4 − group and males in the DR3 − DR4 + group. An association of DPB 1 with IDDM was revealed by an increased frequency overall of DPB 1 ∗0301 and/or DPB 1 ∗0401, being more pronounced in patients diagnosed at >20 years of age. Thus, early age at diagnosis of IDDM is associated with a restricted number of DR and DQ haplotypes. Older age at diagnosis is associated with an increase in heterogeneity of DRB 1 and a decrease in heterogeneity of DPB 1. These findings imply that a limited range of HLA class II peptide complexes determine the age at which IDDM presents clinically, possibly by influencing the nature of β-cell autoimmunity and the rate of progression of β-cell destruction.