title: Preformed circulating HLA-specific memory B cells predict high risk of humoral rejection in kidney transplantation.
abstract: The accurate evaluation of donor-specific antibodies (DSAs) has allowed a precise identification of sensitized patients at risk of antibody-mediated rejection (ABMR). However, the scale of the humoral response is not always fully addressed, as it excludes the complete memory B-cell (mBC) pool such as that caused by antigen-specific mBC. Using a novel B-cell ELISpot assay approach, we assessed circulating mBC frequencies against class I and II HLA antigens in highly sensitized and nonsensitized patients in the waiting list for kidney transplantation. Also, kidney transplant patients undergoing ABMR were evaluated for the presence of donor-specific mBCs both at the time of rejection and before transplantation. For this purpose, 278 target HLA-sp antigens from 70 patients were studied and compared to circulating HLA-sp antibodies. Both class I and II HLA-sp mBC frequencies were identified in highly sensitized individuals but not in nonsensitized and healthy individuals, many years after first sensitization. Also, high donor-specific mBC responses were clearly found both during ABMR and before transplantation, regardless of circulating DSA. The higher the donor-specific mBC response, the more aggressive the allograft rejection. Thus, assessing donor-specific mBC frequencies may be relevant to better refine patient alloimmune-risk stratification, and provides new insight into the mechanisms of the adaptive humoral alloimmune response taking place in kidney transplantation.
authors.affiliation: Experimental Nephrology Laboratory, IDIBELL, Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Lúcia
authors.affiliation: Experimental Nephrology Laboratory, IDIBELL, Barcelona, Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Luque
authors.affiliation: Experimental Nephrology Laboratory, IDIBELL, Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Crespo
authors.affiliation: Renal Transplant Unit, Nephrology Department, Bellvitge University Hospital, Barcelona University, Barcelona, Spain.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Melilli
authors.affiliation: Experimental Nephrology Laboratory, IDIBELL, Barcelona, Spain.|Renal Transplant Unit, Nephrology Department, Bellvitge University Hospital, Barcelona University, Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Cruzado
authors.affiliation: Histocompatibility Unit, Immunology Department, Hospital Clinic, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Martorell
authors.affiliation: Experimental Nephrology Laboratory, IDIBELL, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Jarque
authors.affiliation: Renal Transplant Unit, Nephrology Department, Bellvitge University Hospital, Barcelona University, Barcelona, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Gil-Vernet
authors.affiliation: Renal Transplant Unit, Nephrology Department, Bellvitge University Hospital, Barcelona University, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Manonelles
authors.affiliation: Experimental Nephrology Laboratory, IDIBELL, Barcelona, Spain.|Renal Transplant Unit, Nephrology Department, Bellvitge University Hospital, Barcelona University, Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Grinyó
authors.affiliation: Experimental Nephrology Laboratory, IDIBELL, Barcelona, Spain.|Renal Transplant Unit, Nephrology Department, Bellvitge University Hospital, Barcelona University, Barcelona, Spain.
authors.forename: Oriol
authors.initials: O
authors.lastname: Bestard
mesh_terms: D000328:Adult; D064591:Allografts; D001402:B-Lymphocytes / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology*; D006680:HLA Antigens / Q000097:blood*; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D056724:Immunity, Humoral; D007156:Immunologic Memory; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014850:Waiting Lists
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D007518:Isoantibodies