title: C4d-fixing capability of low-level donor-specific HLA antibodies is not predictive for early antibody-mediated rejection.
abstract: BACKGROUND
  Recent studies indicate that not all low-level donor-specific human leukocyte antigen (HLA) antibodies (HLA-DSA) (i.e., positive by solid-phase assays, negative by complement-dependent cytotoxic-crossmatch) have a detrimental clinical impact. The aim of this study was to investigate whether the pretransplant C4d-fixing capability allows distinguishing harmful from presumably clinically irrelevant HLA-DSA.
  
  
  METHODS
  We retrospectively investigated 64 patients with low-level HLA-DSA detected by single-antigen flow beads (SAFB). Thirty-four of 64 patients (53%) experienced early antibody-mediated rejection (AMR), whereas 30 patients (47%) did not. HLA-DSA characteristics (i.e., number, class, and strength), frequency of retransplants, and immunosuppressive regimens were not different in these two groups. Pretransplant sera were reanalyzed using a modified SAFB assay measuring C4d fixation induced by HLA antibodies.
  
  
  RESULTS
  C4d-fixing HLA-DSA were observed in 11 of 64 patients (17%). AMR occurred in 6 of 11 patients (55%) with C4d-fixing HLA-DSA and in 28 of 53 patients (53%) without C4d-fixing HLA-DSA (P=1.0). Positive C4d staining in peritubular capillaries was detected in 6 of 11 patients (55%) with C4d-fixing HLA-DSA and in 21 of 53 patients (40%) without C4d-fixing HLA-DSA (P=0.50).
  
  
  CONCLUSIONS
  The pretransplant capability of low-level HLA-DSA to trigger C4d fixation in vitro is not predictive for early AMR or C4d deposition in peritubular capillaries in vivo. This argues against pretransplant C4d SAFB testing to define the clinical relevance of low-level HLA-DSA.
authors.affiliation: Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
authors.forename: Gideon
authors.initials: G
authors.lastname: Hönger
authors.forename: Markus
authors.initials: M
authors.lastname: Wahrmann
authors.forename: Patrizia
authors.initials: P
authors.lastname: Amico
authors.forename: Helmut
authors.initials: H
authors.lastname: Hopfer
authors.forename: Georg A
authors.initials: GA
authors.lastname: Böhmig
authors.forename: Stefan
authors.initials: S
authors.lastname: Schaub
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000737:chemistry*; D001706:Biopsy; D002196:Capillaries / Q000276:immunology; D015935:Complement C4b / Q000737:chemistry; D005260:Female; D006084:Graft Rejection; D006680:HLA Antigens / Q000737:chemistry*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000737:chemistry; D012189:Retrospective Studies
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D007074:Immunoglobulin G; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d