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HLA-DR 3 is associated with a more slowly progressive form of type 1 (insulin-dependent) diabetes

J Ludvigsson, U Samuelsson, C Beauforts

    Diabetologia
    |April 1, 1986
    PubMed

    Insights

    Human leukocyte antigen (HLA) typing reveals genetic heterogeneity in Type 1 diabetes. Specific HLA-DR types correlate with disease presentation, severity, and remission, suggesting HLA-DR as a marker for diabetes subtypes.

    Area of Science:

    • Immunogenetics
    • Endocrinology
    • Pediatric Endocrinology

    Background:

    • Type 1 diabetes (T1D) is an autoimmune disease with a significant genetic component.
    • Human leukocyte antigen (HLA) genes are strongly associated with T1D susceptibility.
    • Understanding HLA associations can elucidate disease mechanisms and heterogeneity.

    Purpose of the Study:

    • To investigate the association of specific HLA-DR alleles (DR3, DR4) with clinical presentation and disease course in Type 1 diabetes patients.
    • To explore potential genetic heterogeneity within Type 1 diabetes based on HLA-DR profiles.
    • To determine if HLA-DR typing can serve as a marker for different T1D subtypes.

    Main Methods:

    • Analysis of HLA-DR antigen presence in 745 pediatric patients diagnosed with Type 1 diabetes (age 1-19 years).
    • Correlation of HLA-DR3 and HLA-DR4 presence with patient demographics, age at diagnosis, seasonal incidence, and clinical characteristics at diagnosis (ketonuria, ketoacidosis).
    • Comparison of disease presentation and course between patients with different HLA-DR profiles (DR3 only, DR3/DR4, DR2 without DR3/DR4).

    Main Results:

    • 91% of patients carried HLA-DR3 and/or HLA-DR4.
    • Patients with HLA-DR3 (without DR4) showed more even seasonal onset and lacked specific incidence peaks observed in DR3/DR4 patients.
    • HLA-DR3 patients generally presented with milder disease, less ketonuria, fewer ketoacidotic symptoms, and a higher rate of partial remission. Higher prevalence of HLA-DR4 in girls may explain more severe disease presentation.
    • Geographical similarities in findings were noted between North America and Europe.

    Conclusions:

    • Type 1 diabetes exhibits genetic heterogeneity, with distinct clinical phenotypes associated with specific HLA-DR alleles.
    • HLA-DR typing is a valuable tool for identifying and characterizing these T1D subtypes.
    • These findings support the concept of genetically distinct forms of Type 1 diabetes, influencing disease presentation and progression.

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