title: Progressive autoimmune beta cell insufficiency: occurrence in the absence of high-risk HLA alleles DR3, DR4.
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.
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens; D015802:HLA-DR2 Antigen; D015803:HLA-DR3 Antigen; D015804:HLA-DR4 Antigen; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011236:Prediabetic State / Q000235:genetics* / Q000276:immunology; D012306:Risk
chemical_list: D006684:HLA-DR Antigens; D015802:HLA-DR2 Antigen; D015803:HLA-DR3 Antigen; D015804:HLA-DR4 Antigen; D000949:Histocompatibility Antigens Class II