β-Cell autoantibodies, human leukocyte antigen II alleles, and type 1 diabetes in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by lack of functional products of the auto-immune regulator gene located on chromosome 21q22.3. The patients are at high risk of developing insulin-dependent (type 1) diabetes, but the positive predictive value of GAD65 or islet cell antibodies for type 1 diabetes is only 27%. Autoantibodies against the IA-2 tyrosine phosphatase-like protein (IA-2 ab) or insulin (IAA) have been suggested to be better markers for active β-cell destruction. We studied these antibodies in sera from 60 Finnish patients with APECED, 12 of whom subsequently developed type 1 diabetes. Four (36) of the 11 patients for whom we had prediabetic samples had IA-2 ab, and 4 (36%) had IAA. None of the 48 nondiabetics had IAA, and only 2 (4%) had IA-2 ab. Both had the antibodies for years without diabetes. Thus, IA-2 ab or IAA have a low sensitivity (36%), but high specificity (96% or 100%), with a positive predictive value of 67% for type 1 diabetes in patients with APECED. Data for human leukocyte antigen haplotypes were available for 59 of the patients, including 11 diabetics, and for 8 additional nondiabetic Finnish patients. No association between type 1 diabetes and high risk genotypes was seen. None of the 11 patients with type 1 diabetes, but 15 of the 56 (27%; P < 0.05) nondiabetic patients and 24 of 93 (26%; P < 0.05) of the control subjects had the DQBi*0602 allele, which is considered protective for type 1 diabetes. This is remarkable, as previously no positive or negative associations have been reported for any disease components of APECED with human leukocyte II antigens

Different Ly antigen phenotypes of in vitro induced helper and suppressor cells.

Specific T suppressor cells induced in vitro have a different Ly alloantigen phenotype from T helper cells induced in vitro from the same spleen cell pool. This study demonstrated that specific T suppressor cells differ from specific T helper cells, even if both are induced from the same spleen cell pool, in similar in vitro conditions, and directed to the same antigen, keyhole limpet haemocyanin. This has three implications. First, it demonstrates that the mechanism of specific T cell suppression, in this (but not in the other) model, is not due to excess help. Second, it provides a means of selectively manipulating T cell effects in antibody production (treatment with anti Ly 2 antiserum has been shown to augment helper activity in vitro). Third, the data increase the evidence that differentiated T effector cells have distinctive Ly phenotypes. The relationship of the specific suppressor cells described here to cytotoxic T cells, with the same Ly phenotype, and to nonspecific suppressor cells characterised as Ly 1+2+, remains to be clarified