Islet cell-specific autoantibodies in children with insulin-dependent diabetes mellitus and their siblings at clinical manifestation of the disease. Childhood Diabetes in Finland Study Group.

Abstract

The aim of this work was to characterize both newly diagnosed insulin-dependent diabetic subjects and their siblings with positive tests for islet cell-specific autoantibodies (ICSAA) and to evaluate whether there is an association between the ICSAA levels detected in the diabetic children and siblings. We analysed 781 probands younger than 15 years of age for islet cell antibodies (ICA) and 755 for insulin autoantibodies (IAA) and 610 of their 3-19-year-old non-diabetic siblings for ICA and IAA upon diagnosis of the proband. Islet cell antibodies were observed in 657 of the probands (84.1%) and IAA in 353 (46.8%). The ICA-positive probands were younger in age and had higher IAA levels than the ICA-negative probands, while the IAA-positive probands were younger and had higher levels of ICA than the IAA-negative probands. Islet cell antibodies were detected in 46 (7.5%) and IAA in 16 (2.6%) siblings, and the ICA-positive siblings had higher IAA levels than the ICA-negative siblings. A falling trend was seen in the frequency of ICA > or = 20 Juvenile Diabetes Foundation units in the siblings with decreasing degrees of HLA identity with the index case. Infections during the preceding year, especially respiratory infections, increased the prevalence of both ICA and IAA in the diabetic children at diagnosis and the frequency of IAA in the siblings. There was a significant, although weak, correlation between the IAA levels of the probands and those of their siblings when 594 pairs were tested (r(s) = 0.15; p < 0.001). No association could be seen between the ICA levels of the probands and those of their siblings, not even when including only HLA-identical proband-sib pairs in the analysis. The lack of any relation between ICA levels in the probands and siblings supports the view that there may be multiple exogenous factors capable of inducing ICA formation or else a common factor but variable responsiveness in the index case and the sibling.