title: Non-Complement-Binding De Novo Donor-Specific Anti-HLA Antibodies and Kidney Allograft Survival.
abstract: C1q-binding ability may indicate the clinical relevance of de novo donor-specific anti-HLA antibodies (DSA). This study investigated the incidence and risk factors for the appearance of C1q-binding de novo DSA and their long-term impact. Using Luminex Single Antigen Flow Bead assays, 346 pretransplant nonsensitized kidney recipients were screened at 2 and 5 years after transplantation for de novo DSA, which was followed when positive by a C1q Luminex assay. At 2 and 5 years, 12 (3.5%) and eight (2.5%) patients, respectively, had C1q-binding de novo DSA. De novo DSA mean fluorescence intensity >6237 and >10,000 at 2 and 5 years, respectively, predicted C1q binding. HLA mismatches and cyclosporine A were independently associated with increased risk of C1q-binding de novo DSA. When de novo DSA were analyzed at 2 years, the 5-year death-censored graft survival was similar between patients with C1q-nonbinding de novo DSA and those without de novo DSA, but was lower for patients with C1q-binding de novo DSA (P=0.003). When de novo DSA were analyzed at 2 and 5 years, the 10-year death-censored graft survival was lower for patients with C1q-nonbinding de novo DSA detected at both 2 and 5 years (P<0.001) and for patients with C1q-binding de novo DSA (P=0.002) than for patients without de novo DSA. These results were partially confirmed in two validation cohorts. In conclusion, C1q-binding de novo DSA are associated with graft loss occurring quickly after their appearance. However, the long-term persistence of C1q-nonbinding de novo DSA could lead to lower graft survival.
authors.affiliation: Departments of Immunology, Bordeaux University, Bordeaux, France; National Center for Scientific Research (CNRS), UMR 5164, Bordeaux, France;
authors.forename: Gwendaline
authors.initials: G
authors.lastname: Guidicelli
authors.affiliation: Bordeaux University, Bordeaux, France; National Center for Scientific Research (CNRS), UMR 5164, Bordeaux, France; Nephrology-Transplantation-Dialysis, and.
authors.forename: Florent
authors.initials: F
authors.lastname: Guerville
authors.affiliation: Bordeaux University, Bordeaux, France; Histopathology, Bordeaux University Hospital, Bordeaux, France;
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lepreux
authors.affiliation: Department of Medicine and Immunology, University of Manitoba, Winnipeg, Manitoba, Canada;
authors.forename: Chris
authors.initials: C
authors.lastname: Wiebe
authors.affiliation: Transplantation, Nephrology and Clinical Immunology Department, Lyon University Hospital, Lyon, France; National Institute for Health and Medical Research (INSERM) U1111, Lyon, France; Lyon Est Teaching and Research Unit, Lyon University, Lyon, France; and.
authors.forename: Olivier
authors.initials: O
authors.lastname: Thaunat
authors.affiliation: Histocompatibility Laboratory, French National Blood Service, Lyon, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Dubois
authors.affiliation: Departments of Immunology, Bordeaux University, Bordeaux, France; National Center for Scientific Research (CNRS), UMR 5164, Bordeaux, France;
authors.forename: Jonathan
authors.initials: J
authors.lastname: Visentin
authors.affiliation: Bordeaux University, Bordeaux, France; National Center for Scientific Research (CNRS), UMR 5164, Bordeaux, France; Nephrology-Transplantation-Dialysis, and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelet
authors.affiliation: Transplantation, Nephrology and Clinical Immunology Department, Lyon University Hospital, Lyon, France; National Institute for Health and Medical Research (INSERM) U1111, Lyon, France; Lyon Est Teaching and Research Unit, Lyon University, Lyon, France; and.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Morelon
authors.affiliation: Department of Medicine and Immunology, University of Manitoba, Winnipeg, Manitoba, Canada;
authors.forename: Peter
authors.initials: P
authors.lastname: Nickerson
authors.affiliation: Bordeaux University, Bordeaux, France; National Center for Scientific Research (CNRS), UMR 5164, Bordeaux, France; Nephrology-Transplantation-Dialysis, and.
authors.forename: Pierre
authors.initials: P
authors.lastname: Merville
authors.affiliation: Departments of Immunology, Bordeaux University, Bordeaux, France; National Center for Scientific Research (CNRS), UMR 5164, Bordeaux, France;
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Taupin
authors.affiliation: Bordeaux University, Bordeaux, France; National Center for Scientific Research (CNRS), UMR 5164, Bordeaux, France; Nephrology-Transplantation-Dialysis, and lionel.couzi@chu-bordeaux.fr.
authors.forename: Lionel
authors.initials: L
authors.lastname: Couzi
mesh_terms: D000328:Adult; D064591:Allografts / Q000276:immunology*; D000906:Antibodies / Q000276:immunology*; D000918:Antibody Specificity; D003165:Complement System Proteins / Q000378:metabolism; D005260:Female; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011485:Protein Binding / Q000276:immunology; D012189:Retrospective Studies; D012307:Risk Factors; D014019:Tissue Donors
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D003165:Complement System Proteins
keywords: C1q; complement; de novo donor specific antibodies; graft survival; kidney transplantation