title: Differences in pathologic features and graft outcomes in antibody-mediated rejection of renal allografts due to persistent/recurrent versus de novo donor-specific antibodies.
abstract: Antibody-mediated rejection (ABMR) of renal allografts occurs in two forms. Type 1 ABMR results from persistence and/or a rebound of preexisting donor-specific antibodies in sensitized patients and usually occurs early post-transplantation. Type 2 ABMR is associated with de novo donor-specific antibodies and usually occurs over one year post-transplantation. It is generally accepted that types 1 and 2 also differ with regard to certain pathologic features including the frequencies of C4d positivity and concurrent cell-mediated rejection. However, direct comparison of pathologic, serologic, and clinical features of types 1 and 2 ABMR is lacking. Here we compared these features in 80 cases of ABMR (37 type 1, 43 type 2) diagnosed at our center. Compared with type 1, type 2 ABMR occurred later post-transplantation, was more often associated with donor-specific antibodies against Class II HLA, and was associated with more interstitial fibrosis/tubular atrophy and more frequent cell-mediated rejection, although these did not differ with respect to C4d positivity. By univariate analysis, graft survival was lower with type 2 than type 1 ABMR with borderline significance. Still, among these 80 patients, all but one treated for ABMR following diagnosis, the only two independent predictors of graft failure were at least moderate interstitial fibrosis/tubular atrophy and failure of the donor-specific antibody relative intensity scale score, a measure of the combined strength of all donor-specific antibodies present, to decrease in response to therapy.
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA. Electronic address: mark.haas@cshs.org.
authors.forename: Mark
authors.initials: M
authors.lastname: Haas
authors.affiliation: Biostatistics Core, Research Institute and General Clinical Research Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: James
authors.initials: J
authors.lastname: Mirocha
authors.affiliation: HLA and Immunogenetics Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Reinsmoen
authors.affiliation: Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Ashley A
authors.initials: AA
authors.lastname: Vo
authors.affiliation: Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Jua
authors.initials: J
authors.lastname: Choi
authors.affiliation: Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Kahwaji
authors.affiliation: Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Peng
authors.affiliation: Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA; Transplantation Institute, Loma Linda University Medical Center, Loma Linda, California, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Villicana
authors.affiliation: Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Stanley C
authors.initials: SC
authors.lastname: Jordan
mesh_terms: D000328:Adult; D064591:Allografts; D001284:Atrophy; D001706:Biopsy; D015935:Complement C4b / Q000032:analysis; D005260:Female; D005355:Fibrosis; D006084:Graft Rejection / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D006085:Graft Survival / Q000187:drug effects; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000097:blood*; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D016030:Kidney Transplantation / Q000009:adverse effects*; D015141:Los Angeles; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D012698:Serologic Tests; D013997:Time Factors
chemical_list: D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d
keywords: Banff classification; C4d; antibody-mediated rejection; cell-mediated rejection; donor-specific antibodies; renal transplant