title: Impact of de novo donor-specific anti-HLA antibodies on grafts outcomes in simultaneous pancreas-kidney transplantation.
abstract: De novo donor-specific antibodies (dDSA) relevance in simultaneous pancreas-kidney (SPK) transplantation has been scarcely investigated. We analyzed dDSA relationship with grafts outcomes in a long-term follow-up SPK-transplanted cohort. In 150 patients that received SPK transplant between 2000 and 2013, post-transplant anti-human leukocyte antigen (HLA) antibodies were screened and identified using Luminex-based assays in sera collected at 3, 6, and 12 months, then yearly. dDSA were detected in 22 (14.7%) patients at a median 3.1 years after transplant. Pretransplant anti-HLA sensitization (OR = 4.64), full HLA-DR mismatch (OR = 4.38), and previous acute cellular rejection (OR = 9.45) were significant risk factors for dDSA. dDSA were significantly associated with kidney (in association with acute rejection) and pancreas graft failure. In dDSA+ patients, those with at least one graft failure presented more frequently dDSA against class II or I + II (P = 0.011) and locusDQ (P = 0.043) and had a higher median dDSA number (P = 0.014) and strength (P = 0.030). Median time between dDSA emergence and pancreas and kidney graft failure was 5 and 12 months, respectively. Emergence of dDSA increased the risk of grafts failure in SPK-transplanted patients. Full HLA-DR mismatch was associated with dDSA emergence. dDSA characteristics might help identify patients at a higher risk of graft failure.
authors.affiliation: Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal.|Unit for Multidisciplinary Investigation in Biomedicine (UMIB), Porto, Portugal.
authors.forename: Jorge
authors.initials: J
authors.lastname: Malheiro
authors.affiliation: Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal.|Unit for Multidisciplinary Investigation in Biomedicine (UMIB), Porto, Portugal.
authors.forename: La Salete
authors.initials: LS
authors.lastname: Martins
authors.affiliation: Centro do Sangue e Transplantação do Porto, Porto, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Tafulo
authors.affiliation: Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: Leonídio
authors.initials: L
authors.lastname: Dias
authors.affiliation: Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal.|Unit for Multidisciplinary Investigation in Biomedicine (UMIB), Porto, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Fonseca
authors.affiliation: Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal.|Unit for Multidisciplinary Investigation in Biomedicine (UMIB), Porto, Portugal.
authors.forename: Idalina
authors.initials: I
authors.lastname: Beirão
authors.affiliation: Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal.|Unit for Multidisciplinary Investigation in Biomedicine (UMIB), Porto, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Castro-Henriques
authors.affiliation: Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Cabrita
mesh_terms: D000328:Adult; D005260:Female; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D016030:Kidney Transplantation; D016015:Logistic Models; D008297:Male; D016035:Pancreas Transplantation; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D006684:HLA-DR Antigens; D007518:Isoantibodies
keywords: antibodies anti-HLA; kidney transplant; outcomes; pancreas transplant; survival; type 1 diabetes