T-lymphocyte changes linked to autoantibodies. Association of insulin autoantibodies with CD4+CD45R+ lymphocyte subpopulation in prediabetic subjects.
The onset of insulin-dependent (type I) diabetes is predictable before hyperglycemia by the presence of islet cell autoantibodies (ICAs) and competitive insulin autoantibodies (CIAAs). CIAA+ICA+ first-degree relatives of individuals with type I diabetes have increased numbers of CD4 cells bearing the CD45R antigen and reciprocal depressions of the CD4 cells bearing the CD29 determinant. In addition, depressed CD4/CD8 ratios are present. In this study, we investigated the correlation between autoantibody levels and T-lymphocyte changes in the prediabetic state. The data demonstrate a clear linear relationship between rising CIAA levels, a marker of disease rate, and rising elevations in the CD4+CD45R+/CD4+CD29+ ratio in 37 CIAA+ICA+ and CIAA+ICA- relatives (r = 0.93). In marked contrast, the degree of CD4/CD8 depression found in individuals with prediabetes or long-term diabetes failed to correlate with either CIAA (r = 0.32) or ICA (r = 0.29) levels. The investigation of T-lymphocyte changes in siblings of individuals with type I diabetes with different stable autoantibody patterns (CIAAs and/or ICAs), and thus varying risks for diabetes, revealed differences in the prediabetic groups. Fifteen CIAA+ICA- relatives with high CIAA levels (greater than 80 nU/ml) had high CD4+CD45R+/CD4+CD29+ ratios (P = 0.03) and depressed CD4/CD8 ratios (P = 0.008). In contrast, CIAA+ICA- relatives with low CIAA levels (39-80 nU/ml), and thus low risk of diabetes, had no alteration in their CD4/CD8 ratio (P = 0.75) or CD4+CD45R+/CD4+CD29+ ratio (P = 0.33). Nineteen CIAA-ICA+ siblings with a predicted intermediate risk for diabetes showed heterogeneity in the presence of T-lymphocyte abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)
Faustman
D
D
Massachusetts General Hospital-East, Diabetes Unit, Charlestown 02129.
Schoenfeld
D
D
Ziegler
R
R
D015703:Antigens, CD / Q000032:analysis*; D000943:Antigens, Differentiation / Q000032:analysis*; D001323:Autoantibodies / Q000032:analysis* / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D005190:Family; D006649:Histocompatibility Antigens / Q000032:analysis*; D006801:Humans; D007330:Insulin Antibodies / Q000032:analysis*; D007515:Islets of Langerhans / Q000276:immunology; D017493:Leukocyte Common Antigens; D011236:Prediabetic State / Q000235:genetics / Q000276:immunology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D001323:Autoantibodies; D015704:CD4 Antigens; D006649:Histocompatibility Antigens; D007330:Insulin Antibodies; C024211:islet cell antibody; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1