IN-VITRO STUDY OF NGAL IMMUNOMODULATORY EFFECT IN HEMODIALYSIS AND HYPERIMMUNIZED PATIENTS

Background: In recent years, an increasing number of patients waiting for kidney transplant, showed the presence of alloantibodies against HLA antigens, and non-HLA. Evidence demonstrates the contribution of regulatory T cells (Treg) in modulating the immune response in different animal models and in clinical transplant, to suggest their potential use as markers of tolerance, rejection or prediction of organ transplant outcome. We have previously provided in vitro evidence that NGAL (neutrophil gelatinase associated lipocalin), a known biomarker of renal injury, is able to induce immune tolerance by upregulating HLA-G expression and expansion of T regulatory cells in normal subjects. In this study, we evaluated the effect of NGAL on expression of HLA-G and influence on Treg populations in hemodialysis and hyperimmune patients. Methods: We enrolled 30 subjects divided in 3 groups: 10 healthy subjects, 10 uremic patients on hemodialysis and 10 hyperimmunized patients. We carried out isolation and characterization of immunophenotypic lymphocyte population Treg from peripheral blood mononuclear cells (PBMCs). Results: Following treatment with increased doses of NGAL (80–640 ng/ml), an increased expression of HLA-G was observed in the population of CD4+ CD25+ FOXP3+ in patients on hemodialysis. This increase is also proportional to the percentage of Treg themselves in PBMCs and comparable to healthy controls.