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Signs of ß-Cell Autoimmunity in Nondiabetic Schoolchildren

A comparison between Russian Karelia with a low incidence of type 1 diabetes and Finland with a high incidence rate

¹ Department of Virology, University of Tampere Medical School, Tampere, Finland
² Department of Pediatrics, University of Petrozavodsk, Petrozavodsk, Russia
³ Department of Clinical Microbiology, Center of Laboratory Medicine, Tampere University Hospital, Tampere, Finland
⁴ Department of Pediatrics, University of Oulu, Oulu, Finland
⁵ Department of Clinical Microbiology, University of Kuopio, Kuopio, Finland
⁶ Immunogenetics Laboratory, Department of Virology, University of Turku, Turku, Finland
⁷ Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
⁸ Department of Pediatrics, Tampere University Hospital, Tampere, Finland

Address correspondence and reprint requests to Mikael Knip, MD, PhD, Hospital for ChildrenAdolescents, University of Helsinki, P.O. Box 281, FIN-00029 HUCH, Helsinki, Finland. E-mail: mikael.knip{at}hus.fi

OBJECTIVE—We sought to study the prevalence of autoantibodies to various islet cell antigens in the background population of two neighboring countries with a sixfold difference in the incidence of type 1 diabetes.

RESEARCH DESIGN AND METHODS—Serum samples were obtained from 3,652 nondiabetic schoolchildren in Finland and from 1,988 schoolchildren in the adjacent Karelian Republic of Russia. The Karelian children were divided into three groups (Finns/Karelians, Russians, and others) based on the ethnic background of their mother. The samples were analyzed for islet cell antibodies (ICAs), insulin autoantibodies (IAAs), GAD antibodies (GADAs), and the tyrosine phosphatase-like insulinoma antigen 2 (IA-2A) protein and HLA class II genotypes.

RESULTS—The frequency of ICAs, IAAs, and GADAs did not differ significantly between the Karelian (3.5, 0.6, and 0.9%, respectively) and Finnish children (2.8, 0.9, and 0.5%, respectively). Similarly, the frequency of multiple (2) autoantibodies was similar in both countries (0.5 vs. 0.6%). The frequency of IA-2A was, however, four times higher in Finland (0.6 vs. 0.15% in Russian Karelia; P = 0.03). There were no significant differences in autoantibody prevalence among the three ethnic groups in Russian Karelia. There was a falling frequency of GADAs and of positivity for multiple autoantibodies along with decreasing HLA-conferred disease susceptibility among the Finnish schoolchildren.

CONCLUSIONS—These data indicate that ß-cell autoimmunity among schoolchildren is as frequent in Russian Karelia as in Finland, although the incidence of clinical type 1 diabetes is six times higher in Finland. However, in contrast to this general trend, IA-2As were more common in Finland. Since IA-2As usually appear late in the preclinical process, this suggests that progressive ß-cell autoimmunity is more rare in Russian Karelia.

Abbreviations: DASP, Diabetes Autoantibody Standardization Program • GADA, GAD antibody • IAA, insulin autoantibody • IA-2A, tyrosine phosphatase-like insulinoma antigen 2 • ICA, islet cell antibody • JDFU, Juvenile Diabetes Foundation units

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