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Understanding the Correlation Between DSA, Complement Activation, and Antibody-Mediated Rejection in Heart Transplant Recipients.
Zhang, Qiuheng; Hickey, Michelle; Drogalis-Kim, Diana; Zheng, Ying; Gjertson, David; Cadeiras, Martin; Khuu, Tam; Baas, Arnold S; Depasquale, Eugene C; Halnon, Nancy J; Perens, Gregory; Alejos, Juan; Cruz, Daniel; Ali, Nsair; Shemin, Richard; Kwon, Murray; Fishbein, Michael C; Ardehali, Abbas; Deng, Mario; Reed, Elaine F.
Afiliação
  • Zhang Q; UCLA Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
  • Hickey M; UCLA Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
  • Drogalis-Kim D; Rainbow Babies and Children's Hospital in Cleveland, OH.
  • Zheng Y; UCLA Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
  • Gjertson D; UCLA Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
  • Cadeiras M; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
  • Khuu T; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
  • Baas AS; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
  • Depasquale EC; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
  • Halnon NJ; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
  • Perens G; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
  • Alejos J; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
  • Cruz D; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
  • Ali N; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
  • Shemin R; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
  • Kwon M; Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
  • Fishbein MC; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
  • Ardehali A; Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
  • Deng M; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
  • Reed EF; UCLA Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
Transplantation ; 102(10): e431-e438, 2018 10.
Article em En | MEDLINE | ID: mdl-29916988
ABSTRACT

BACKGROUND:

Donor-specific HLA antibodies (DSA) are associated with increased rates of rejection and of graft failure in cardiac transplantation. The goal of this study was to determine the association of preformed and posttransplant development of newly detected DSA (ndDSA) with antibody-mediated rejection (AMR) and characterize the clinical relevance of complement-activating DSA in heart allograft recipients.

METHODS:

The study included 128 adult and 48 pediatric heart transplant patients transplanted between 2010 and 2013. Routine posttransplant HLA antibody testing was performed by IgG single-antigen bead test. The C3d single-antigen bead assay was used to identify complement-activating antibodies. Rejection was diagnosed using International Society for Heart and Lung Transplantation criteria.

RESULTS:

In this study, 22 patients were transplanted with preexisting DSA, and 43 patients developed ndDSA posttransplant. Pretransplant (P < 0.05) and posttransplant (P < 0.001) ndDSA were associated with higher incidence of AMR. Patients with C3d + DSA had significantly higher incidence of AMR compared with patients with no DSA (P < 0.001) or patients with C3d-DSA (P = 0.02). Nine (36%) of 25 patients with AMR developed transplant coronary artery disease compared with 17 (15.9%) of 107 patients without AMR (P < 0.05). Among the 47 patients who received ventricular assistant device (VAD), 7 of 9 VAD+ patients with preformed DSA experienced AMR compared with 7 of 38 VAD+ patients without preformed DSA, indicating presensitization to donor HLA significantly increased the risk of AMR (P < 0.01).

CONCLUSIONS:

Preformed and posttransplant ndDSA were associated with AMR. C3d + DSA correlates with complement deposition on the graft and higher risk of AMR which may permit the application of personalized immunotherapy targeting the complement pathway.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transplante de Coração / Ativação do Complemento / Rejeição de Enxerto / Cardiopatias / Antígenos HLA / Isoanticorpos Tipo de estudo: Incidence_studies / Prognostic_studies Limite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male / Middle aged Idioma: En Revista: Transplantation Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Canadá
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transplante de Coração / Ativação do Complemento / Rejeição de Enxerto / Cardiopatias / Antígenos HLA / Isoanticorpos Tipo de estudo: Incidence_studies / Prognostic_studies Limite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male / Middle aged Idioma: En Revista: Transplantation Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Canadá