caa a22 4500 47577230X CHVBK 20180406123620.0 cr unu---uuuuu 170329e20000401xx s 000 0 eng 10.1007/s001250051329 doi (NATIONALLICENCE)springer-10.1007/s001250051329 Stability of autoantibodies and their relation to genetic and metabolic markers of Type I diabetes in initially unaffected schoolchildren [Elektronische Daten] [P. Kulmala, J. Rahko, K. Savola, P. Vähäsalo, R. Veijola, M. Sjöroos, A. Reunanen, J. Ilonen, M. Knip] Aims/hypothesis. To study temporal changes in positivity for autoantibodies associated with Type I (insulin-dependent) diabetes mellitus and the relations between these antibodies, HLA-DQB1-risk markers and first-phase insulin response (FPIR) in non-diabetic schoolchildren.¶Methods. The stability of the antibody status over 2 years was assessed in 104 schoolchildren initially positive for islet cell antibodies (ICA) or antibodies to the 65 000 Mr isoform of the glutamic acid decarboxylase (GADA) or both and in 104 antibody-negative control children matched for sex, age and place of residence. All children were also studied for their first-phase insulin response and HLA-DQB1 alleles on the second occasion.¶Results. On the second occasion 3 of the 98 initially ICA-positive children, 3/13 of those positive for antibodies to the IA-2 protein (IA-2A), 1/17 GADA-positive and 2/7 of those positive for insulin autoantibodies (IAA) tested negative for these antibodies. Children with IA-2A, GADA, IAA and multiple ( ≥ 2) antibodies had significantly lower first-phase insulin responses than the control children. In contrast, these responses did not differ between subjects with and without specific HLA-DQB1-risk alleles or genotypes. Of the six subjects with a considerably reduced first-phase insulin response three had multiple antibodies on both occasions but none of them had a DQB1 genotype conferring increased diabetes risk. Two subjects progressed to Type I diabetes within 3.4 years of follow-up, both of them having multiple antibodies and a considerably reduced first-phase insulin response but neither of them having a DQB1-risk genotype.¶Conclusions/interpretation. Positivity for diabetes-associated autoantibodies is a relatively stable phenomenon in unaffected schoolchildren, although conversion to seronegativity can occur occasionally. Our observations also indicate that DQB1 alleles associated with decreased susceptibility to Type I diabetes do not protect from impaired beta-cell function or from progression to overt disease in initially unaffected schoolchildren. [Diabetologia (2000) 43: 457-464] Springer-Verlag Berlin Heidelberg, 2000 Keywords Autoantibodies, FPIR, HLA, schoolchildren, Type I diabetes nationallicence Kulmala P. Department of Paediatrics, University of Oulu, Finland, FI aut Rahko J. Department of Paediatrics, University of Oulu, Finland, FI aut Savola K. Department of Paediatrics, University of Oulu, Finland, FI aut Vähäsalo P. Department of Paediatrics, University of Oulu, Finland, FI aut Veijola R. Department of Paediatrics, University of Oulu, Finland, FI aut Sjöroos M. Turku Immunology Centre and Department of Virology, University of Turku, Finland, FI aut Reunanen A. The National Public Health Institute, Helsinki, Finland, FI aut Ilonen J. Turku Immunology Centre and Department of Virology, University of Turku, Finland, FI aut Knip M. Medical School, University of Tampere and Department of Paediatrics Tampere University Hospital, Finland, FI aut https://doi.org/10.1007/s001250051329 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051329 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kulmala P. Department of Paediatrics, University of Oulu, Finland, FI aut NATIONALLICENCE 700 1- Rahko J. Department of Paediatrics, University of Oulu, Finland, FI aut NATIONALLICENCE 700 1- Savola K. Department of Paediatrics, University of Oulu, Finland, FI aut NATIONALLICENCE 700 1- Vähäsalo P. Department of Paediatrics, University of Oulu, Finland, FI aut NATIONALLICENCE 700 1- Veijola R. Department of Paediatrics, University of Oulu, Finland, FI aut NATIONALLICENCE 700 1- Sjöroos M. Turku Immunology Centre and Department of Virology, University of Turku, Finland, FI aut NATIONALLICENCE 700 1- Reunanen A. The National Public Health Institute, Helsinki, Finland, FI aut NATIONALLICENCE 700 1- Ilonen J. Turku Immunology Centre and Department of Virology, University of Turku, Finland, FI aut NATIONALLICENCE 700 1- Knip M. Medical School, University of Tampere and Department of Paediatrics Tampere University Hospital, Finland, FI aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer