title: Pre-transplant soluble CD30 in combination with total DSA but not pre-transplant C1q-DSA predicts antibody-mediated graft loss in presensitized high-risk kidney transplant recipients.
abstract: Presensitized kidney transplant recipients are at high-risk for early antibody-mediated rejection. We studied the impact of pre- and post-transplant donor-specific human leukocyte antigen (HLA) antibodies (DSA) and T-cell-activation on the occurrence of antibody-mediated rejection episodes (AMR) and graft loss (AMR-GL) in a unique cohort of 80 desensitized high-risk kidney transplant recipients. Patients with pre-transplant DSA demonstrated more AMR episodes than patients without DSA, but did not show a significantly increased rate of AMR-GL. The rates of AMR and AMR-GL were not significantly increased in patients with complement split product (C1q)-binding pre-transplant DSA. Pre-transplant C1q-DSA became undetectable post-transplant in 11 of 13 (85%) patients; 2 (18%) of these 11 patients showed AMR but no AMR-GL. In contrast, the post-transplant presence of C1q-DSA was associated with significantly higher rates of AMR (86 vs 33 vs 0%; P < 0.001) and AMR-GL (86 vs 0 vs 0%; log-rank P < 0.001) compared with post-transplant DSA without C1q-binding or the absence of DSA. Patients with both pre-transplant DSA and evidence of pre-transplant T-cell-activation as indicated by soluble CD30-positivity showed a significantly increased risk for AMR-GL [HR = 11.1, 95% confidence interval (CI) = 1.68-73.4; log-rank P = 0.013]. In these high-risk patients, AMR-GL was associated with total DSA in combination with T-cell-activation pre-transplant, and de novo or persistent C1q-binding DSA post-transplant.
authors: Division of Nephrology, University Hospital of Heidelberg, Heidelberg, Germany.
authors: S M
authors: SM
authors: Schaefer
authors: Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
authors: C
authors: C
authors: Süsal
authors: Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
authors: G
authors: G
authors: Opelz
authors: Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
authors: B
authors: B
authors: Döhler
authors: Division of Nephrology, University Hospital of Heidelberg, Heidelberg, Germany.
authors: L E
authors: LE
authors: Becker
authors: Division of Nephrology, University Hospital of Heidelberg, Heidelberg, Germany.
authors: K
authors: K
authors: Klein
authors: Division of Nephrology, University Hospital of Heidelberg, Heidelberg, Germany.
authors: S
authors: S
authors: Sickmüller
authors: Department of Pathology, University of Heidelberg, Heidelberg, Germany.
authors: R
authors: R
authors: Waldherr
authors: Department of Pathology, University of Heidelberg, Heidelberg, Germany.
authors: S
authors: S
authors: Macher-Goeppinger
authors: Division of Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
authors: P
authors: P
authors: Schemmer
authors: Division of Nephrology, University Hospital of Heidelberg, Heidelberg, Germany.
authors: J
authors: J
authors: Beimler
authors: Division of Nephrology, University Hospital of Heidelberg, Heidelberg, Germany.
authors: M
authors: M
authors: Zeier
authors: Division of Nephrology, University Hospital of Heidelberg, Heidelberg, Germany.
authors: C
authors: C
authors: Morath
mesh_terms: D000328:Adult; D000368:Aged; D003172:Complement C1 / Q000276:immunology / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000097:blood* / Q000276:immunology; D006801:Humans; D007518:Isoantibodies / Q000097:blood* / Q000276:immunology; D017730:Ki-1 Antigen / Q000097:blood* / Q000276:immunology; D016030:Kidney Transplantation; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D057234:Preoperative Period; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
chemical_list: D003172:Complement C1; D007518:Isoantibodies; D017730:Ki-1 Antigen
keywords: B-cell; C1q; antibody-mediated rejection; donor-specific antibodies; human leukocyte antigen; increased soluble CD30; kidney; rejection; transplantation