caa a22 4500 475771079 CHVBK 20180406123617.0 cr unu---uuuuu 170329e20000601xx s 000 0 eng 10.1007/s001250051372 doi (NATIONALLICENCE)springer-10.1007/s001250051372 Th1-like dominance in high-risk first-degree relatives of Type I diabetic patients [Elektronische Daten] [M.G.E. Karlsson, S. Sederholm Lawesson, J. Ludvigsson] Aims/hypothesis. The humoral part of the immune system, including autoantibodies, is known to predict manifest Type I (insulin-dependent) diabetes mellitus in first-degree relatives but the cell-mediated immune process preceding the manifest disease still is not known. The aim of this investigation was to estimate the immunological balance of Th-like lymphocytes (Th1/Th2) in high-risk first-degree relatives of Type I diabetic children.¶Methods. Peripheral blood mononuclear cells (PBMC) from 21 healthy high-risk first-degree relatives (ICA ≥ 20) were examined and compared with the response seen in PBMC from children with newly diagnosed Type I diabetes and healthy control subjects of similar age, sex and HLA-type. Expression of interleukin-4 (IL-4) and interferon-γ (IFN-γ) mRNA were determined by RT-PCR and as protein by ELISPOT after stimulation with specific epitopes of GAD65 (a. a. 247-279, 509-528, 524-543), bovine serum albumin, the ABBOS peptide (a. a. 152-169) and insulin.¶Results. High-risk relatives had a high ratio of IFN-γ:IL-4 compared with both diabetic children (p = 0.0005) and healthy control subjects (p = 0.004). Production of IFN-γ seen in high-risk relatives was negatively correlated to production of GADA (r = -0.44, p = 0.05). The high concentration of IFN-γ from high-risk relatives, decreased after stimulation with peptides of GAD65, the ABBOS peptide, BSA and insulin. Increased secretion of IL-4 was observed after stimulation with two peptides of GAD65 (a. a. 509-528 and 524-543), the ABBOS peptide and insulin.¶Conclusion/interpretation. Overwhelming production of IFN-γ seen in peripheral blood mononuclear cells from high-risk first-degree relatives of children with Type I diabetes suggests a Th1-like immune deviation in the prediabetic phase. [Diabetologia (2000) 43: 742-749] Springer-Verlag Berlin Heidelberg, 2000 Keywords Type I diabetes, Th-lymphocyte, high-risk relatives, IFN-γ, IL-4, GAD65, ABBOS, BSA, insulin, GADA nationallicence Karlsson M.G.E. Department of Health and Environment, Division of Paediatrics, Faculty of Health Sciences, Linköping University, Linköping, Sweden, SE aut Sederholm Lawesson S. Department of Health and Environment, Division of Paediatrics, Faculty of Health Sciences, Linköping University, Linköping, Sweden, SE aut Ludvigsson J. Department of Health and Environment, Division of Paediatrics, Faculty of Health Sciences, Linköping University, Linköping, Sweden, SE aut https://doi.org/10.1007/s001250051372 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051372 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Karlsson M.G.E. Department of Health and Environment, Division of Paediatrics, Faculty of Health Sciences, Linköping University, Linköping, Sweden, SE aut NATIONALLICENCE 700 1- Sederholm Lawesson S. Department of Health and Environment, Division of Paediatrics, Faculty of Health Sciences, Linköping University, Linköping, Sweden, SE aut NATIONALLICENCE 700 1- Ludvigsson J. Department of Health and Environment, Division of Paediatrics, Faculty of Health Sciences, Linköping University, Linköping, Sweden, SE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer