Th1-like dominance in high-risk first-degree relatives of Type I diabetic patients
2000 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 43, no 6, 742-749 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2000. Vol. 43, no 6, 742-749 p.
Type I diabetes, Th-lymphocyte, high-risk relatives, IFN-γ, IL-4, GAD65, ABBOS, BSA, insulin, GADA.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-25985DOI: 10.1007/s001250051372Local ID: 10437OAI: oai:DiVA.org:liu-25985DiVA: diva2:246533