Variability of Immune Biomarkers with the Graft Function in Kidney Transplant Patients in India, an Observational Prospective Cohort Study

Abstract

In renal transplantation (RT), the major issue is to maintain the immune homeostasis, limiting graft rejection (GR), and promoting transplant tolerance. A total of 70 subjects of chronic kidney disease patients on maintenance haemodialysis, opted for RT and 20 controls were recruited. The Tregs% (CD4+CD25+), concentration of cytokines IL –10 and IL 17 were measured in pre-and post-transplant at a defined timelines with stable graft function (SGF) and with GR for two years, using flow cytometer and sandwich ELISA method. With SGF, Tregs% Baseline [8.5 (6.5–10.7) vs. HCs [14.25 (13–18), p < 0.01)], at Baseline vs. six months [11.54 (8.9–15)], p < 0.001); At Baseline [3.05 (1.05–5.2) vs. GR 8.5 (6.5–10.7), p < 0.05]. Serum IL 10 baseline [3.6 (2.56–4.6) vs. HC (6.4 (4.8-9.8), p<0.001]. Serum IL 17 levels at baseline [120 (92 - 176) vs. HC [20.88 (18-55), p<0.05], day four vs. baseline [180 (160.5-257.45); p<0.05], day 90 vs. baseline [53.3 (48-100), p< 0.05] and this was maintained for two years, with GR vs. baseline [190 (105-372); p<0.05]. ROC analysis of Tregs% (AUC of 0.758 and a p – value of <0.05), IL-10 (AUC of 0.8 and a p – value of 0.117), IL-17 (AUC of 0.937 and a p – value of <0.05). With SGF, Tregs % increased from 6 months, IL-17 decreased from 3 months, IL-10 did not show changes and continued till two years; with GR, Tregs% decreased from baseline, IL-10 did not show changes, and IL-17 increased due to high inflammation. ROC analysis showed that the Tregs% and IL-17 are better predictors of graft outcome. However, the association between biomarkers with graft function couldn’t be evaluated which needs further studies.