P1617RENAL TRANSPLANT PATIENTS HARBOR NEUTROPHILS SECRETING B-CELL ACTIVATING FACTOR (BAFF) WHICH CAN BE SUPPRESSED BY MTOR INHIBITORS

Abstract

Abstract Background and Aims B cell activating factor (BAFF) is a cytokine which drives B cell survival and maturation. Several studies have shown that elevated BAFF levels in renal transplant patients are associated with increased risk for the development of donor specific antibodies and antibody mediated rejection. It was the aim of this study to investigate neutrophils as cellular source of BAFF in renal transplant patients. Method Neutrophils (NT) were freshly isolated from whole blood of healthy controls (HC) and renal transplant patients (RTX). After isolation, purity of neutrophils was usually above 98%. Neutrophils were stimulated with LPS or TNFα in presence of Granulocyte-colony stimulating factor (GCSF) or Granulocyte macrophage colony-stimulating factor (GMCSF). In selected conditions, FK506 or rapamycin was added. Supernatants were harvested after 20 hours of culture and BAFF levels were determined by ELISA. Results GCSF/TNFα and GCSF/LPS were the most potent stimuli leading to BAFF secretion of NT in HC (403 ±64 pg/ml and 421 ±69 pg/ml). NT derived RTX showed similar capacity to secrete BAFF as compared to HC (GCSF/TNFα: 515 ±31 pg/ml and GCSF/LPS: 539.4 ±36 pg/ml). Treatment of cultures with rapamycin reduced BAFF levels (515 ±100 pg/ml vs. 348 ±27 pg/ml, p<0.001). Treatment with FK506 was less efficacious (515 ±31 pg/ml vs. 465 ±31 pg/ml, p=0.01). Conclusion NT may enhance of B cell maturation and survival via BAFF. BAFF-secretion by NT can be suppressed with mTOR inhibitors. In renal transplantation, NT might promote formation of allo-antibodies and drive antibody mediated rejection.