title: Antibody-Mediated Rejection Due to Preexisting versusDe NovoDonor-Specific Antibodies in Kidney Allograft Recipients.
abstract: Antibody-mediated rejection (ABMR) can occur in patients with preexisting anti-HLA donor-specific antibodies (DSA) or in patients who developde novoDSA. However, how these processes compare in terms of allograft injury and outcome has not been addressed. From a cohort of 771 kidney biopsy specimens from two North American and five European centers, we performed a systematic assessment of clinical and biologic parameters, histopathology, circulating DSA, and allograft gene expression for all patients with ABMR (n=205). Overall, 103 (50%) patients had preexisting DSA and 102 (50%) hadde novoDSA. Compared with patients with preexisting DSA ABMR, patients withde novoDSA ABMR displayed increased proteinuria, more transplant glomerulopathy lesions, and lower glomerulitis, but similar levels of peritubular capillaritis and C4d deposition.De novoDSA ABMR was characterized by increased expression of IFNγ-inducible, natural killer cell, and T cell transcripts, but less expression of AKI transcripts compared with preexisting DSA ABMR. The preexisting DSA ABMR had superior graft survival compared with thede novoDSA ABMR (63% versus 34% at 8 years after rejection, respectively;P<0.001). After adjusting for clinical, histologic, and immunologic characteristics and treatment, we identifiedde novoDSA ABMR (hazard ratio [HR], 1.82 compared with preexisting DSA ABMR; 95% confidence interval [95% CI], 1.07 to 3.08;P=0.03); low eGFR (<30 ml/min per 1.73 m2) at diagnosis (HR, 3.27; 95% CI, 1.48 to 7.23;P<0.001); ≥0.30 g/g urine protein-to-creatinine ratio (HR, 2.44; 95% CI, 1.47 to 4.09;P<0.001); and presence of cg lesions (HR, 2.25; 95% CI, 1.34 to 3.79;P=0.002) as the main independent determinants of allograft loss. Our findings support the transplant of kidneys into highly sensitized patients and should encourage efforts to monitor patients forde novoDSA.
authors.affiliation: Paris Translational Research Center for Organ Transplantation, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche-S970, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Aubert
authors.affiliation: Paris Translational Research Center for Organ Transplantation, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche-S970, Paris, France; alexandreloupy@gmail.com.|Paris Descartes University, Sorbonne Paris Cite, Paris, France.|Kidney Transplantation Department and.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Loupy
authors.affiliation: Department of Laboratory Medicine and Pathology and.|Alberta Transplant Applied Genomics Centre, Edmonton, Alberta, Canada.
authors.forename: Luis
authors.initials: L
authors.lastname: Hidalgo
authors.affiliation: Department of Pathology, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Duong van Huyen
authors.affiliation: Department of Nephrology, Sherbrooke University, Sherbrooke, Québec, Canada; and.
authors.forename: Sarah
authors.initials: S
authors.lastname: Higgins
authors.affiliation: Paris Translational Research Center for Organ Transplantation, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche-S970, Paris, France.|Department of Nephrology and Organ Transplantation, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Viglietti
authors.affiliation: Paris Translational Research Center for Organ Transplantation, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche-S970, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Jouven
authors.affiliation: Paris Translational Research Center for Organ Transplantation, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche-S970, Paris, France.|Department of Nephrology and Organ Transplantation, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Glotz
authors.affiliation: Paris Translational Research Center for Organ Transplantation, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche-S970, Paris, France.|Paris Descartes University, Sorbonne Paris Cite, Paris, France.|Kidney Transplantation Department and.
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.affiliation: Paris Translational Research Center for Organ Transplantation, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche-S970, Paris, France.|Department of Nephrology and Organ Transplantation, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Carmen
authors.initials: C
authors.lastname: Lefaucheur
authors.affiliation: Alberta Transplant Applied Genomics Centre, Edmonton, Alberta, Canada.|Department of Medicine, Division of Nephrology and Transplant Immunology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Philip F
authors.initials: PF
authors.lastname: Halloran
mesh_terms: D064591:Allografts; D000906:Antibodies / Q000276:immunology*; D000918:Antibody Specificity; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000276:immunology / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D014019:Tissue Donors
chemical_list: D000906:Antibodies; D006680:HLA Antigens
keywords: antibody-mediated rejection; donor-specific anti-HLA antibody; kidney transplantation; microscope; molecular; transplant outcomes