title: De Novo Donor-Specific HLA Antibodies Developing Early or Late after Transplant Are Associated with the Same Risk of Graft Damage and Loss in Nonsensitized Kidney Recipients.
abstract: De novo posttransplant donor-specific HLA-antibody (dnDSA) detection is now recognized as a tool to identify patients at risk for antibody-mediated rejection (AMR) and graft loss. It is still unclear whether the time interval from transplant to DSA occurrence influences graft damage. Utilizing sera collected longitudinally, we evaluated 114 consecutive primary pediatric kidney recipients grafted between 2002 and 2013 fordnDSA occurrence by Luminex platform.dnDSAs occurred in 39 patients at a median time of 24.6 months. In 15 patients,dnDSAs developed within 1 year (early-onsetgroup), while the other 24 seroconverted after the first posttransplant year (late-onsetgroup). The two groups were comparable when considering patient- and transplant-related factors, as well as DSA biological properties, including C1q and C3d complement-binding ability. Only recipient age at transplant significantly differed in the two cohorts, with younger patients showing earlierdnDSA development. Late AMR was diagnosed in 47% of theearlygroup and in 58% of thelategroup. Graft loss occurred in 3/15 (20%) and 4/24 (17%) patients inearly-andlate-onsetgroups, respectively (p= ns). In our pediatric kidney recipients,dnDSAs predict AMR and graft loss irrespective of the time elapsed between transplantation and antibody occurrence.
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto G. Gaslini, Genova, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Cioni
authors.affiliation: Clinical Nephrology Unit and Transplant Immunology Research Laboratory, Department of Internal Medicine, University of Genova and IRCCS San Martino University Hospital IST, Genova, Italy.
authors.forename: Arcangelo
authors.initials: A
authors.lastname: Nocera
authors.affiliation: Transplantation Immunology, IRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Innocente
authors.affiliation: Clinical Nephrology Unit and Transplant Immunology Research Laboratory, Department of Internal Medicine, University of Genova and IRCCS San Martino University Hospital IST, Genova, Italy.
authors.forename: Augusto
authors.initials: A
authors.lastname: Tagliamacco
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto G. Gaslini, Genova, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Trivelli
authors.affiliation: Pediatric Hematology/Oncology and Cell Factory, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Basso
authors.affiliation: Pediatric Hematology/Oncology and Cell Factory, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Quartuccio
authors.affiliation: Vascular and Endovascular Unit and Kidney Transplant Surgery Unit, University of Genova, IRCCS San Martino University Hospital IST, Genova, Italy.
authors.forename: Iris
authors.initials: I
authors.lastname: Fontana
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto G. Gaslini, Genova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Magnasco
authors.affiliation: Transplantation Immunology, IRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Drago
authors.affiliation: Pediatric Hematology/Oncology and Cell Factory, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Gurrado
authors.affiliation: Pediatric Hematology/Oncology and Cell Factory, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Guido
authors.affiliation: Pediatric Hematology/Oncology and Cell Factory, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Compagno
authors.affiliation: Clinical Nephrology Unit and Transplant Immunology Research Laboratory, Department of Internal Medicine, University of Genova and IRCCS San Martino University Hospital IST, Genova, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Garibotto
authors.affiliation: Biometry and Statistics Service, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Catherine
authors.initials: C
authors.lastname: Klersy
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto G. Gaslini, Genova, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Verrina
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto G. Gaslini, Genova, Italy.
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
authors.affiliation: Transplantation Immunology, IRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Cardillo
authors.affiliation: Pediatric Hematology/Oncology and Cell Factory, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Patrizia
authors.identifier: 0000-0001-5964-0553
authors.initials: P
authors.lastname: Comoli
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto G. Gaslini, Genova, Italy.
authors.forename: Fabrizio
authors.identifier: 0000-0003-2377-8774
authors.initials: F
authors.lastname: Ginevri
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D015922:Complement C1q / Q000276:immunology; D015933:Complement C3d / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000097:blood* / Q000276:immunology*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008137:Longitudinal Studies; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies; D015922:Complement C1q; D015933:Complement C3d