title: Clinical Outcome of Patients With De Novo C1q-Binding Donor-Specific HLA Antibodies After Renal Transplantation.
abstract: De novo donor specific anti-HLA antibodies (dnDSA) may cause graft loss in renal transplant recipients. The capability to bind the complement may help to stratify the risk for inferior outcomes associated with dnDSA. We developed a modified C1q-binding assay and hypothesized that C1q-binding dnDSA could differentiate between indolent and harmful dnDSA causing antibody-mediated rejection (AMR) and graft loss.
  
  
  
  We retrospectively identified 59 renal transplant recipients who developed dnDSA and had serum available and complete follow-up. All patients were analyzed for C1q-binding dnDSA at the time of dnDSA detection, and 1-year later or at time of AMR. AMR-positive patients were also tested 6 to 12 months before the event if IgG dnDSA was present.
  
  
  
  Thirty-seven of 59 dnDSA patients developed AMR during 5.9 ± 3.1 years follow-up. AMR-positive patients had more dnDSA with a significant higher frequency of class I, a higher frequency and a higher mean fluorescence intensity value of C1q-dnDSA at all time-points. Death-censored AMR-free and allograft survivals were significantly lower in C1q-dnDSA patients. In multivariate analysis, C1q-dnDSA was an independent risk factor for AMR.
  
  
  
  C1q-binding dnDSA is associated with inferior outcomes, yet not in all patients. Nevertheless, C1q-dnDSA was shown to be an independent risk factor of AMR and graft loss and may be a useful tool to stratify the immunological risk for AMR.
authors.affiliation: 1 Department of Nephrology, Campus Charité Mitte, Charité Universitätsmedizin, Berlin, Germany. 2 HLA Laboratory, Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Germany. 3 INSERM, UMR1098, Federation Hospitalo-Universitaire INCREASE, Besançon, France. 4 Université de Franche-Comté, Faculté de Médecine et de Pharmacie, Besançon, France. 5 Department of Hospital Pharmacy, Erasmus University Medical Centre, Rotterdam, The Netherlands. 6 Department of Pathology, Campus Charite Mitte, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Jamal
authors.initials: J
authors.lastname: Bamoulid
authors.forename: Afaf
authors.initials: A
authors.lastname: Roodenburg
authors.forename: Oliver
authors.initials: O
authors.lastname: Staeck
authors.forename: Kaiyin
authors.initials: K
authors.lastname: Wu
authors.forename: Birgit
authors.initials: B
authors.lastname: Rudolph
authors.forename: Susanne
authors.initials: S
authors.lastname: Brakemeier
authors.forename: Fabian
authors.initials: F
authors.lastname: Halleck
authors.forename: Lukas
authors.initials: L
authors.lastname: Lehner
authors.forename: Constanze
authors.initials: C
authors.lastname: Schönemann
authors.forename: Nils
authors.initials: N
authors.lastname: Lachmann
authors.forename: Klemens
authors.initials: K
authors.lastname: Budde
mesh_terms: D000328:Adult; D000368:Aged; D016009:Chi-Square Distribution; D015922:Complement C1q / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015200:Fluoroimmunoassay; D006084:Graft Rejection / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011485:Protein Binding; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012698:Serologic Tests; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; D007074:Immunoglobulin G; D007518:Isoantibodies; D015922:Complement C1q