Enhanced Donor Antigen Presentation by B Cells Predicts Acute Cellular Rejection and Late Outcomes After Transplantation.


Journal

Transplantation direct
ISSN: 2373-8731
Titre abrégé: Transplant Direct
Pays: United States
ID NLM: 101651609

Informations de publication

Date de publication:
Mar 2024
Historique:
received: 31 05 2023
revised: 16 10 2023
accepted: 11 11 2023
medline: 28 2 2024
pubmed: 28 2 2024
entrez: 28 2 2024
Statut: epublish

Résumé

Enhanced B-cell presentation of donor alloantigen relative to presentation of HLA-mismatched reference alloantigen is associated with acute cellular rejection (ACR), when expressed as a ratio called the antigen presenting index (API) in an exploratory cohort of liver and intestine transplant (LT and IT) recipients. To test clinical performance, we measured the API using the previously described 6-h assay in 84 LT and 54 IT recipients with median age 3.3 y (0.05-23.96). Recipients experiencing ACR within 60 d after testing were termed rejectors. We first confirmed that B-cell uptake and presentation of alloantigen induced and thus reflected the alloresponse of T-helper cells, which were incubated without and with cytochalasin and primaquine to inhibit antigen uptake and presentation, respectively. Transplant recipients included 76 males and 62 females. Rejectors were tested at median 3.6 d before diagnosis. The API was higher among rejectors compared with nonrejectors (2.2 ± 0.2 versus 0.6 ± 0.04, Enhanced donor antigen presentation by circulating B cells predicts rejection after liver or intestine transplantation as well as higher incidence of DSA and graft loss late after transplantation.

Sections du résumé

Background UNASSIGNED
Enhanced B-cell presentation of donor alloantigen relative to presentation of HLA-mismatched reference alloantigen is associated with acute cellular rejection (ACR), when expressed as a ratio called the antigen presenting index (API) in an exploratory cohort of liver and intestine transplant (LT and IT) recipients.
Methods UNASSIGNED
To test clinical performance, we measured the API using the previously described 6-h assay in 84 LT and 54 IT recipients with median age 3.3 y (0.05-23.96). Recipients experiencing ACR within 60 d after testing were termed rejectors.
Results UNASSIGNED
We first confirmed that B-cell uptake and presentation of alloantigen induced and thus reflected the alloresponse of T-helper cells, which were incubated without and with cytochalasin and primaquine to inhibit antigen uptake and presentation, respectively. Transplant recipients included 76 males and 62 females. Rejectors were tested at median 3.6 d before diagnosis. The API was higher among rejectors compared with nonrejectors (2.2 ± 0.2 versus 0.6 ± 0.04,
Conclusions UNASSIGNED
Enhanced donor antigen presentation by circulating B cells predicts rejection after liver or intestine transplantation as well as higher incidence of DSA and graft loss late after transplantation.

Identifiants

pubmed: 38414976
doi: 10.1097/TXD.0000000000001589
pmc: PMC10898653
doi:

Types de publication

Journal Article

Langues

eng

Pagination

e1589

Informations de copyright

Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.

Déclaration de conflit d'intérêts

The antigen presenting test is based on US Patent 10222374, inventors: R.S. and C.A., Assignee: University of Pittsburgh of the Commonwealth System of Higher Education, Pittsburgh, PA, and licensed to Plexision, Inc., Pittsburgh 15224, in which the University and R.S. holds equity. C.A. is a consultant to licensee without other financial relationships. Disclosed conflicts of interest have been managed in accordance with the University of Pittsburgh’s policies and procedures. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. All other authors have nothing to disclose. The other authors declare no conflicts of interest.

Auteurs

Chethan Ashokkumar (C)

Department of Surgery, Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh and the University of Pittsburgh, PA.

Mylarappa Ningappa (M)

Department of Surgery, Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh and the University of Pittsburgh, PA.

Vikram Raghu (V)

Division of Pediatric Gastroenterology, Hepatology, and Nutrition, UPMC Children's Hospital Pittsburgh, PA.

George Mazariegos (G)

Department of Surgery, Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh and the University of Pittsburgh, PA.

Brandon W Higgs (BW)

Department of Surgery, Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh and the University of Pittsburgh, PA.

Paul Morgan (P)

Department of Surgery, Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh and the University of Pittsburgh, PA.

Lisa Remaley (L)

Department of Surgery, Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh and the University of Pittsburgh, PA.

Tamara Fazzolare Martin (T)

Department of Surgery, Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh and the University of Pittsburgh, PA.

Pamela Holzer (P)

Department of Surgery, Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh and the University of Pittsburgh, PA.

Kevin Trostle (K)

Department of Surgery, Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh and the University of Pittsburgh, PA.

Qingyong Xu (Q)

Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA.

Adriana Zeevi (A)

Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA.

James Squires (J)

Division of Pediatric Gastroenterology, Hepatology, and Nutrition, UPMC Children's Hospital Pittsburgh, PA.

Kyle Soltys (K)

Department of Surgery, Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh and the University of Pittsburgh, PA.

Simon Horslen (S)

Division of Pediatric Gastroenterology, Hepatology, and Nutrition, UPMC Children's Hospital Pittsburgh, PA.

Ajai Khanna (A)

Department of Surgery, Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh and the University of Pittsburgh, PA.

Armando Ganoza (A)

Department of Surgery, Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh and the University of Pittsburgh, PA.

Rakesh Sindhi (R)

Department of Surgery, Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh and the University of Pittsburgh, PA.

Classifications MeSH