title: Circulating NK-cell subsets in renal allograft recipients with anti-HLA donor-specific antibodies.
abstract: Detection of posttransplant donor-specific anti-HLA antibodies (DSA) constitutes a risk factor for kidney allograft loss. Together with complement activation, NK-cell antibody-dependent cell mediated cytotoxicity (ADCC) has been proposed to contribute to the microvascular damage associated to humoral rejection. In the present observational exploratory study, we have tried to find a relationship of circulating donor-specific and non donor-specific anti-HLA antibodies (DSA and HLA non-DSA) with peripheral blood NK-cell subsets and clinical features in 393 renal allograft recipients. Multivariate analysis indicated that retransplantation and pretransplant sensitization were associated with detection of posttransplant DSA. Recipient female gender, DR mismatch and acute rejection were significantly associated with posttransplant DSA compared to HLA non-DSA. In contrast with patients without detectable anti-HLA antibodies, DSA and HLA non-DSA patients displayed lower proportions of NK-cells, associated with increased CD56(bright) and NKG2A(+) subsets, the latter being more marked in DSA cases. These differences appeared unrelated to retransplantation, previous acute rejection or immunosuppressive therapy. Although preliminary and observational in nature, our results suggest that the assessment of the NK-cell immunophenotype may contribute to define signatures of alloreactive humoral responses in renal allograft recipients.
authors: Department of Nephrology, Hospital del Mar, Barcelona, Spain; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
authors: M
authors: M
authors: Crespo
authors: J
authors: J
authors: Yelamos
authors: D
authors: D
authors: Redondo
authors: A
authors: A
authors: Muntasell
authors: M J
authors: MJ
authors: Perez-Saéz
authors: M
authors: M
authors: López-Montañés
authors: C
authors: C
authors: García
authors: A
authors: A
authors: Torio
authors: M
authors: M
authors: Mir
authors: J J
authors: JJ
authors: Hernández
authors: M
authors: M
authors: López-Botet
authors: J
authors: J
authors: Pascual
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D016030:Kidney Transplantation; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D014184:Transplantation, Homologous
chemical_list: D001323:Autoantibodies; D006680:HLA Antigens
keywords: Alloantibody; clinical research/practice; histocompatibility; immunosuppressive regimens; kidney transplantation/nephrology; natural killer (NK) cells/NK receptors; rejection: antibody-mediated (ABMR); translational research/science