Peripheral blood mononuclear cells of patients with latent autoimmune diabetes secrete higher levels of pro- & anti-inflammatory cytokines compared to those with type-1 diabetes mellitus following in vitro stimulation with β-cell autoantigens

摘要

Background & objectives: Type-1 diabetes mellitus (T1DM) and latent autoimmune diabetes in adults (LADA) share similar pathological features but differ in age of onset and progression. There is a scarcity of information on differences in CD4+ T-cell responses, particularly, cytokine secretion, between the two forms of autoimmune diabetes. Here proliferative potential and concentration of pro- and anti-inflammatory cytokines secreted by peripheral blood mononuclear cells (PBMCs) of T1DM and LADA patients were compared, after in vitro stimulation with β-cell autoantigens. Methods: A total of 19 patients with LADA, 37 with T1DM and 20 healthy controls were compared on the basis of lymphocyte proliferation and secretion of pro- and anti-inflammatory cytokines belonging to different T-helper types after in vitro stimulation of PBMCs with insulin and glutamic acid decarboxylase 65 (GAD65). Results: Following insulin stimulation, LADA group secreted higher concentration of interleukin-17 (IL-17) (P=0.02) and had higher proportion of interferon gamma (IFN-γ) secretors (P P=0.02). Proportion of responders , as well as levels of secreted IL-10, were significantly higher in LADA than T1DM group, following stimulation with both insulin (P=0.01) and GAD65 (P=0.03). A significant positive correlation was observed between body mass index and IL-17 levels (r=0.41, P=0.04) and fasting plasma C-peptide with IL-10 levels (r=0.37, P=0.04). Interpretation & conclusions: There are differences in the portfolio of cytokine secretion in diabetic subjects with varying rates of β-cell destruction as LADA subjects secrete higher levels of both pro- and anti-inflammatory cytokines on exposure to β-cell autoantigens, thus highlighting another distinguishing feature in the pathophysiology of the two forms of autoimmune diabetes.