title: Use of complement binding assays to assess the efficacy of antibody mediated rejection therapy and prediction of graft survival in kidney transplantation.
abstract: BACKGROUND
  The Luminex® single antigen bead assay (SAB) is the method of choice for monitoring the treatment for antibody-mediated rejection (AMR). A ⩾50% reduction of the dominant donor-specific antibody (IgG-DSA) mean fluorescence intensity (MFI) has been associated with improved kidney allograft survival, and C1q-fixing DSA activity is associated with poor outcomes in patients with AMR. We aimed to investigate if C1q-DSA can be used as a reliable predictor of response to therapy and allograft survival in patients with biopsy-proven AMR.
  
  
  METHODS
  We tested pre- and post-treatment sera of 30 kidney transplant patients receiving plasmapheresis and low-dose IVIG for biopsy-proven AMR. IgG-DSA and C1q-DSA MFI were measured and correlated with graft loss or survival. Patients were classified as nonresponders (NR) when treatment resulted in <50% reduction in MFI of IgG-DSA and/or C1q-DSA was detectable following therapy.
  
  
  RESULTS
  Differences in the percentage of patients deemed NR depended upon the end-point criterion (73% by reduction in IgG-DSA MFI vs. 50% by persistent C1q-DSA activity). None of the seven patients with <50% reduction of IgG-DSA but non-detectable C1q-DSA-fixing activity after therapy experienced graft loss, suggesting that C1q-DSA activity may better correlate with response. Reduction of C1q-DSA activity predicted graft survival better than IgG-DSA in the univariate Cox analysis (20.1% vs. 5.9% in NR; log-rank P-value=0.0147).
  
  
  CONCLUSIONS
  A rapid reduction of DSA concentration below the threshold required for complement activation is associated with better graft survival, and C1q-DSA is a better predictor of outcomes than IgG-DSA MFI reduction.
authors.affiliation: Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA. Electronic address: dramon@stanford.edu.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Ramon
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
authors.forename: Yihung
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy Services, University of Michigan School of Medicine, Ann Arbor, MI, USA.
authors.forename: TrisAnn
authors.initials: T
authors.lastname: Rendulic
authors.affiliation: Department of Pharmacy Services, University of Michigan School of Medicine, Ann Arbor, MI, USA.
authors.forename: Jeong M
authors.initials: JM
authors.lastname: Park
authors.affiliation: Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA.
authors.forename: Randall S
authors.initials: RS
authors.lastname: Sung
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
authors.forename: Milagros
authors.initials: M
authors.lastname: Samaniego
mesh_terms: D000328:Adult; D000920:Antibody-Dependent Cell Cytotoxicity; D015922:Complement C1q / Q000276:immunology / Q000378:metabolism*; D015941:Complement Hemolytic Activity Assay; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000175:diagnosis* / Q000401:mortality / Q000517:prevention & control; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007518:Isoantibodies / Q000378:metabolism*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies; D015922:Complement C1q