ASSOCIATION OF IA-2 AUTOANTIBODIES WITH HLA DR4 PHENOTYPES IN IDDM

Insulin, glutamate decarboxylase (GAD) and the protein tyrosine phosph atase-like molecule IA-2 are major targets of humoral autoimmunity in insulin-dependent diabetes mellitus (IDDM). These autoantibodies are h eterogeneous with respect to age and patient human leukocyte antigen ( HLA) phenotype. We have previously demonstrated that GAD and IA-2 anti bodies potentially identify different subsets of IDDM patients. The ai m of this study was to determine whether GAD and IA-2 autoantibodies w ere associated with different HLA DR phenotypes. We studied 160 patien ts with IDDM onset before age 16 years. At disease onset serum was tes ted for GAD and IA-2 antibodies by immunoprecipitation of in vitro-tra nslated S-35-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 H LA DR4 (p(c) < 0.0001). In contrast, GAD antibodies were more prevalen t (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 ass ociated with HLA class II alleles.