TNF-α pathway and T-cell immunity are activated early during the development of diabetic nephropathy in Type II Diabetes Mellitus

Aim of the present study was to investigate the possible involvement of TNF-alpha signaling pathway and T-lymphocyte activation in DN. Eighty-two diabetic patients [39 male, age 69.5(56-78)years] were divided into three groups, according to Albumin/Creatinine ratio (ACR) levels, Group I (ACR < 30 mu g/mg), Group II (ACR 30-300 mu g/mg), Group III (ACR > 300 mu g/mg). Urinary Tumor Necrosis Factor-alpha (TNF-alpha), and serum TNF-alpha, TNF-receptor 1 (TNFR1), TNFR2, B7-1, CD28, Cytoxic T-Lymphocyte-Associated protein-4 (CTLA4), were estimated. There were significant differences between Groups I, II, III regarding the concentration of urinary TNF-alpha (p < .001), serum TNFR1 (p < .001), serum TNFR2(p < .001), CTLA4 (p < .001) and CD28(p = .034). In multivariate analysis, independent parameters correlated with ACR were serum TNFR1 (p = .003), TNFR2 (p = .012) and urinary TNF-alpha (p = .015) levels. There was a significant correlation between markers of T-cell activation and TNF-alpha signaling pathway activation. Activation of TNF-alpha signaling pathway and T-lymphocytes seem to synergize and participate in the development of DN in type II DM.