title: Evaluation of C1q Status and Titer of De Novo Donor-Specific Antibodies as Predictors of Allograft Survival.
abstract: De novo donor-specific antibodies (dnDSAs) that develop after renal transplantation are independent predictors of allograft loss. However, it is unknown if dnDSA C1q status or titer at the time of first detection can independently predict allograft loss. In a consecutive cohort of 508 renal transplant recipients, 70 developed dnDSAs. Histologic and clinical outcomes were correlated with the C1q assay or dnDSA titer. C1q positivity correlated with dnDSA titer (p < 0.01) and mean fluorescence intensity (p < 0.01) and was more common in class II versus class I dnDSAs (p < 0.01). C1q status correlated with tubulitis (p = 0.02) and C4d status (p = 0.03) in biopsies at the time of dnDSA development, but not T cell-mediated rejection (TCMR) or antibody-mediated rejection (ABMR). De novo DSA titer correlated with Banff g, i, t, ptc, C4d scores, TCMR (p < 0.01) and ABMR (p < 0.01). Post-dnDSA graft loss was observed more frequently in recipients with C1q-positve dnDSA (p < 0.01) or dnDSA titer ≥ 1:1024 (p ≤ 0.01). However, after adjustment for clinical phenotype and nonadherence in multivariate models, neither C1q status nor dnDSA titer were independently associated with allograft loss, questioning the utility of these assays at the time of dnDSA development.
authors.affiliation: Department of Medicine, University of Manitoba, Winnipeg, Canada.|Diagnostic Services of Manitoba, Winnipeg, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Wiebe
authors.affiliation: Department of Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: A J
authors.initials: AJ
authors.lastname: Gareau
authors.affiliation: Diagnostic Services of Manitoba, Winnipeg, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Pochinco
authors.affiliation: Diagnostic Services of Manitoba, Winnipeg, Canada.|Department of Pathology, University of Manitoba, Winnipeg, Canada.
authors.forename: I W
authors.initials: IW
authors.lastname: Gibson
authors.affiliation: Department of Medicine, University of Manitoba, Winnipeg, Canada.|Department of Immunology, University of Manitoba, Winnipeg, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Ho
authors.affiliation: Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada.
authors.forename: P E
authors.initials: PE
authors.lastname: Birk
authors.affiliation: Department of Pediatrics, University of British Columbia, Vancouver, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Blydt-Hansen
authors.affiliation: Department of Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Karpinski
authors.affiliation: Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Goldberg
authors.affiliation: Department of Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Storsley
authors.affiliation: Department of Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: D N
authors.initials: DN
authors.lastname: Rush
authors.affiliation: Department of Medicine, University of Manitoba, Winnipeg, Canada.|Diagnostic Services of Manitoba, Winnipeg, Canada.|Department of Immunology, University of Manitoba, Winnipeg, Canada.
authors.forename: P W
authors.initials: PW
authors.lastname: Nickerson
mesh_terms: D000328:Adult; D064591:Allografts; D015922:Complement C1q / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000209:etiology*; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D007676:Kidney Failure, Chronic / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D014019:Tissue Donors; D066027:Transplant Recipients
chemical_list: D007518:Isoantibodies; D015922:Complement C1q
keywords: alloantibody; antibody biology; clinical research/practice; immunobiology; kidney (allograft) function/dysfunction; kidney transplantation/nephrology; organ transplantation in general; rejection: antibody-mediated (ABMR); rejection: subclinical; translational research/science