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  • Title: Progressive autoimmune beta cell insufficiency: occurrence in the absence of high-risk HLA alleles DR3, DR4.
    Author: Eisenbarth GS, Srikanta S, Fleischnick E, Ganda OP, Jackson RA, Brink SJ, Soeldner JS, Yunis EJ, Alper C.
    Journal: Diabetes Care; 1985; 8(5):477-80. PubMed ID: 3876922.
    Abstract:
    In a prospective screening program for type I diabetes mellitus, we identified a unique family in which several members (mother and three siblings) expressed an unusual set of HLA-DR alleles (DR2+, DR3/4-) and were in different phases of immunologically mediated islet beta cell dysfunction. Immunologic and/or clinical manifestations of type I diabetes were absent in all siblings not sharing both HLA haplotypes in common with the proband. This article illustrates: the clinical utility of prospective family screening for predictive markers, such as islet cell antibodies, progressive autoimmune beta cell destruction can occur in the absence of the "high-risk" alleles HLA-DR3 and DR4, and HLA identity with the proband, rather than specific HLA alleles, i.e., presence of DR3, DR4 and absence of DR2, is an essential factor.
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