title: Clinical relevance of pretransplant anti-HLA donor-specific antibodies: does C1q-fixation matter?
abstract: Anti-HLA donor-specific antibodies (DSA) identified by single antigen bead array (SAB) are questioned for their excess in sensitivity and lack of event prediction after transplantation.
  
  
  METHODS
  We retrospectively evaluated specific types of preformed DSA (class I, class II or C1q-fixing) and their impact on graft survival. Kidney transplantations performed across negative CDC-crossmatch were included (n=355). Anti-HLA antibodies were tested using SAB to identify DSA and their capacity to fix C1q.
  
  
  RESULTS
  Twenty-eight patients with pretransplant DSA(+) with MFI>2000 were selected to assess C1q fixation. DSA were C1q+ in 15 patients and C1q- in 13, without significant differences in demographics, acute rejection, graft loss or renal function. The maximum MFI of DSA in patients with C1q-fixing DSA was significantly higher (p=0.008). Patients with DSA class-I suffered more antibody-mediated rejection (AMR) and had worse graft survival than class-II. The capacity of DSA I to fix C1q did not correlate with rejection, graft function or graft loss.
  
  
  CONCLUSIONS
  C1q testing in pretransplant sera with DSA was unable to predict acute antibody-mediated rejection or early graft loss, but the presence of DSA class I compared to DSA only class II did. Despite non-fixing complement in vitro, pretransplant C1q-negative DSA I can mediate rejection and graft loss.
authors.affiliation: Department of Nephrology, Hospital del Mar, Paseo Marítimo 25-29, 08003 Barcelona, Spain; Institute Hospital del Mar for Medical Research (IMIM), Paseo Marítimo 25-29, 08003 Barcelona, Spain. Electronic address: mcrespo@hospitaldelmar.cat.
authors.forename: Marta
authors.initials: M
authors.lastname: Crespo
authors.forename: Alberto
authors.initials: A
authors.lastname: Torio
authors.forename: Virginia
authors.initials: V
authors.lastname: Mas
authors.forename: Dolores
authors.initials: D
authors.lastname: Redondo
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Pérez-Sáez
authors.forename: Marisa
authors.initials: M
authors.lastname: Mir
authors.forename: Anna
authors.initials: A
authors.lastname: Faura
authors.forename: Rita
authors.initials: R
authors.lastname: Guerra
authors.forename: Olga
authors.initials: O
authors.lastname: Montes-Ares
authors.forename: Maria D
authors.initials: MD
authors.lastname: Checa
authors.forename: Julio
authors.initials: J
authors.lastname: Pascual
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D003167:Complement Activation; D015922:Complement C1q / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006084:Graft Rejection / Q000097:blood* / Q000209:etiology / Q000276:immunology; D006085:Graft Survival; D006680:HLA Antigens / Q000097:blood* / Q000276:immunology; D006801:Humans; D007518:Isoantibodies / Q000097:blood* / Q000276:immunology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies; D015922:Complement C1q
keywords: AMR; Antibody-mediated rejection; CDC; Complement; Complement-dependent cytotoxic; DSA; Donor-specific antibodies; Donor-specific antibody; HLA antibody; IQR; Interquartilic range; Kidney transplantation; MFI; Mean fluorescence index; SAB; Single antigen bead array