title: C1q binding is not an independent risk factor for kidney allograft loss after an acute antibody-mediated rejection episode: a retrospective cohort study.
abstract: After kidney transplantation, C4d is an incomplete marker of acute antibody-mediated rejection (AMR) and C1q-binding donor-specific antibodies (DSA) have been associated with allograft survival. However, the impact on allograft survival of C1q+ DSA after clinical AMR has not been studied yet. We analysed retrospectively in clinical AMR C4d staining and C1q-binding impact on allograft survival. We compared clinical, histological and serological features of C4d- and C4d+ AMR, C1q+ and C1q- DSA AMR and analysed C4d and C1q-binding impact on allograft survival. Among 500 for-cause kidney allograft biopsies, 48 fulfilled AMR criteria. C4d+ AMR [N = 18 (37.5%)] have significantly higher number class I DSA (P = 0.02), higher microvascular score (P = 0.02) and more transplant glomerulopathy (P = 0.04). C1q+ AMR [N = 20 (44%)] presented with significantly more class I and class II DSA (P = 0.005 and 0.04) and C4d+ staining (P = 0.01). Graft losses were significantly higher in the C4d+ group (P = 0.04) but similar in C1q groups. C4d+ but not C1q+ binding was an independent risk factor for graft loss [HR = 2.65; (1.11-6.34); P = 0.028]. In our cohort of clinical AMR, C4d+ staining but not C1q+ binding is an independent risk factor for graft loss. Allograft loss and patient survival were similar in C1q+ and C1q- AMR.
authors.affiliation: APHP (Assistance Publique-Hôpitaux de Paris), Pathology Department, Groupe Hospitalier Henri-Mondor/Albert Chenevier, Créteil, France.|DHU (Département Hospitalo-Universitaire) VIC (Virus-Immunité-Cancer), IMRB (Institut Mondor de Recherche Biomédicale), Equipe 21, INSERM U 955, Université Paris-Est-Créteil (UPEC), Créteil, France.
authors.forename: Anissa
authors.initials: A
authors.lastname: Moktefi
authors.affiliation: AP-HP (Assistance Publique-Hôpitaux de Paris), Public Health Department, Groupe Hospitalier Henri-Mondor/Albert Chenevier, Créteil, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Parisot
authors.affiliation: APHP (Assistance Publique-Hôpitaux de Paris), Pathology Department, Groupe Hospitalier Henri-Mondor/Albert Chenevier, Créteil, France.|DHU (Département Hospitalo-Universitaire) VIC (Virus-Immunité-Cancer), IMRB (Institut Mondor de Recherche Biomédicale), Equipe 21, INSERM U 955, Université Paris-Est-Créteil (UPEC), Créteil, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Desvaux
authors.affiliation: AP-HP (Assistance Publique-Hôpitaux de Paris), Public Health Department, Groupe Hospitalier Henri-Mondor/Albert Chenevier, Créteil, France.|DHU (Département Hositalo-Universitaire) A-TVB, IMRB (Institut Mondor de Recherche Biomédicale)- EA 7376 CEpiA (Clinical Epidemiology And Ageing Unit), Université Paris-Est-Créteil, UPEC, Créteil, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Canoui-Poitrine
authors.affiliation: AP-HP (Assistance Publique-Hôpitaux de Paris), Pathology Department, Tenon Hospital, Paris, France.|INSERM UMRS_1155, Université Pierre et Marie Curie, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Brocheriou
authors.affiliation: INSERM UMRS_1155, Université Pierre et Marie Curie, Paris, France.|AP-HP (Assistance Publique-Hôpitaux de Paris), Intensive Care Nephrology and Renal Transplantation, Tenon Hospital, Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Peltier
authors.affiliation: DHU (Département Hospitalo-Universitaire) VIC (Virus-Immunité-Cancer), IMRB (Institut Mondor de Recherche Biomédicale), Equipe 21, INSERM U 955, Université Paris-Est-Créteil (UPEC), Créteil, France.|AP-HP (Assistance Publique-Hôpitaux de Paris), Nephrology and Renal Transplantation Department, Institut Francilien de Recherche en Néphrologie et Transplantation (IFRNT), Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Créteil, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Audard
authors.affiliation: AP-HP (Assistance Publique-Hôpitaux de Paris), Nephrology and Renal Transplantation Department, Institut Francilien de Recherche en Néphrologie et Transplantation (IFRNT), Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Créteil, France.
authors.forename: Tomek
authors.initials: T
authors.lastname: Kofman
authors.affiliation: AP-HP (Assistance Publique-Hôpitaux de Paris), Immunology and Histocompatibility Department, Saint Louis Hospital, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Suberbielle
authors.affiliation: DHU (Département Hospitalo-Universitaire) VIC (Virus-Immunité-Cancer), IMRB (Institut Mondor de Recherche Biomédicale), Equipe 21, INSERM U 955, Université Paris-Est-Créteil (UPEC), Créteil, France.|AP-HP (Assistance Publique-Hôpitaux de Paris), Nephrology and Renal Transplantation Department, Institut Francilien de Recherche en Néphrologie et Transplantation (IFRNT), Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Créteil, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lang
authors.affiliation: INSERM UMRS_1155, Université Pierre et Marie Curie, Paris, France.|AP-HP (Assistance Publique-Hôpitaux de Paris), Intensive Care Nephrology and Renal Transplantation, Tenon Hospital, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Rondeau
authors.affiliation: DHU (Département Hospitalo-Universitaire) VIC (Virus-Immunité-Cancer), IMRB (Institut Mondor de Recherche Biomédicale), Equipe 21, INSERM U 955, Université Paris-Est-Créteil (UPEC), Créteil, France.|AP-HP (Assistance Publique-Hôpitaux de Paris), Nephrology and Renal Transplantation Department, Institut Francilien de Recherche en Néphrologie et Transplantation (IFRNT), Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Créteil, France.|AP-HP, CIC-BT 504, Créteil, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Grimbert
authors.affiliation: DHU (Département Hospitalo-Universitaire) VIC (Virus-Immunité-Cancer), IMRB (Institut Mondor de Recherche Biomédicale), Equipe 21, INSERM U 955, Université Paris-Est-Créteil (UPEC), Créteil, France.|AP-HP (Assistance Publique-Hôpitaux de Paris), Nephrology and Renal Transplantation Department, Institut Francilien de Recherche en Néphrologie et Transplantation (IFRNT), Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Créteil, France.|AP-HP, CIC-BT 504, Créteil, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Matignon
mesh_terms: D000328:Adult; D015331:Cohort Studies; D015922:Complement C1q / Q000378:metabolism*; D015935:Complement C4b / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000209:etiology* / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000378:metabolism*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D014019:Tissue Donors
chemical_list: D007518:Isoantibodies; D010446:Peptide Fragments; D015922:Complement C1q; D015935:Complement C4b; C032261:complement C4d
keywords: C1q-binding DSA; C4d staining; allograft survival; antibody-mediated rejection; kidney transplantation