title: Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant.
abstract: The natural history for patients with de novo donor-specific antibodies (dnDSA) and the risk factors for its development have not been well defined. Furthermore, clinical and histologic correlation with serologic data is limited. We studied 315 consecutive renal transplants without pretransplant DSA, with a mean follow-up of 6.2 ± 2.9 years. Protocol (n = 215) and for cause (n = 163) biopsies were analyzed. Solid phase assays were used to screen for dnDSA posttransplant. A total of 47 out of 315 (15%) patients developed dnDSA at a mean of 4.6 ± 3.0 years posttransplant. Independent predictors of dnDSA were HLA-DRβ1 MM > 0 (OR 5.66, p < 0.006); and nonadherence (OR 8.75, p < 0.001); with a strong trend toward clinical rejection episodes preceding dnDSA (OR 1.57 per rejection episode, p = 0.061). The median 10-year graft survival for those with dnDSA was lower than the No dnDSA group (57% vs. 96%, p < 0.0001). Pathology consistent with antibody-mediated injury can occur and progress in patients with dnDSA in the absence of graft dysfunction and furthermore, nonadherence and cellular rejection contribute to dnDSA development and progression to graft loss.
authors.affiliation: Department of Medicine and Immunology, University of Manitoba, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Wiebe
authors.forename: I W
authors.initials: IW
authors.lastname: Gibson
authors.forename: T D
authors.initials: TD
authors.lastname: Blydt-Hansen
authors.forename: M
authors.initials: M
authors.lastname: Karpinski
authors.forename: J
authors.initials: J
authors.lastname: Ho
authors.forename: L J
authors.initials: LJ
authors.lastname: Storsley
authors.forename: A
authors.initials: A
authors.lastname: Goldberg
authors.forename: P E
authors.initials: PE
authors.lastname: Birk
authors.forename: D N
authors.initials: DN
authors.lastname: Rush
authors.forename: P W
authors.initials: PW
authors.lastname: Nickerson
mesh_terms: D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D006085:Graft Survival / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate; D014019:Tissue Donors
chemical_list: D000949:Histocompatibility Antigens Class II; D007518:Isoantibodies