Summary
Insulin, glutamate decarboxylase (GAD) and the protein tyrosine phosphatase-like molecule IA-2 are major targets of humoral autoimmunity in insulin-dependent diabetes mellitus (IDDM). These autoantibodies are heterogeneous with respect to age and patient human leukocyte antigen (HLA) phenotype. We have previously demonstrated that GAD and IA-2 antibodies potentially identify different subsets of IDDM patients. The aim of this study was to determine whether GAD and IA-2 autoantibodies were associated with different HLA DR phenotypes. We studied 160 patients with IDDM onset before age 16 years. At disease onset serum was tested for GAD and IA-2 antibodies by immunoprecipitation of in vitro-translated35S-methionine labelled recombinant proteins. IA-2 antibodies were significantly associated with HLA DR4: 67 (86 %) of 78 patients with HLA DR4 vs 31 (38 %) of 82 non-DR4 patients had IA-2 antibodies (p c<0.0001) and IA-2 antibody levels were higher in patients with HLA DR4 (p c<0.0001). In contrast, GAD antibodies were more prevalent (p c<0.05) and antibody levels highest (p c<0.01) in patients with HLA DR3 phenotypes. These data provide further evidence that, in IDDM, production and titre of major autoantibody specificities are associated with HLA class II alleles.
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Abbreviations
- IDDM:
-
Insulin-dependent diabetes mellitus
- GAD:
-
glutamic acid decarboxylase
- IAA:
-
insulin autoantibodies
- HLA:
-
human leukocyte antigen
- CI:
-
confidence interval
- ICA:
-
islet cell antibodies
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Genovese, S., Bonfanti, R., Bazzigaluppi, E. et al. Association of IA-2 autoantibodies with HLA DR4 phenotypes in IDDM. Diabetologia 39, 1223–1226 (1996). https://doi.org/10.1007/BF02658510
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DOI: https://doi.org/10.1007/BF02658510