Discovery of non-HLA antibodies associated with cardiac allograft rejection and development and validation of a non-HLA antigen multiplex panel: From bench to bedside.
autoantibody
autoantigen
clinical research/practice
heart transplantation/cardiology
histocompatibility
immunogenetics
microarray/protein array
organ transplantation in general
rejection
translational research/science
Journal
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
ISSN: 1600-6143
Titre abrégé: Am J Transplant
Pays: United States
ID NLM: 100968638
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
10
10
2019
revised:
04
03
2020
accepted:
05
03
2020
pubmed:
19
3
2020
medline:
22
6
2021
entrez:
19
3
2020
Statut:
ppublish
Résumé
We analyzed humoral immune responses to nonhuman leukocyte antigen (HLA) after cardiac transplantation to identify antibodies associated with allograft rejection. Protein microarray identified 366 non-HLA antibodies (>1.5 fold, P < .5) from a discovery cohort of HLA antibody-negative, endothelial cell crossmatch-positive sera obtained from 12 cardiac allograft recipients at the time of biopsy-proven rejection. From these, 19 plasma membrane proteins and 10 autoantigens identified from gene ontology analysis were combined with 48 proteins identified through literature search to generate a multiplex bead array. Longitudinal sera from a multicenter cohort of adult cardiac allograft recipients (samples: n = 477 no rejection; n = 69 rejection) identified 18 non-HLA antibodies associated with rejection (P < .1) including 4 newly identified non-HLA antigenic targets (DEXI, EMCN, LPHN1, and SSB). CART analysis showed 5/18 non-HLA antibodies distinguished rejection vs nonrejection. Antibodies to 4/18 non-HLA antigens synergize with HLA donor-specific antibodies and significantly increase the odds of rejection (P < .1). The non-HLA panel was validated using an independent adult cardiac transplant cohort (n = 21 no rejection; n = 42 rejection, >1R) with an area under the curve of 0.87 (P < .05) with 92.86% sensitivity and 66.67% specificity. We conclude that multiplex bead array assessment of non-HLA antibodies identifies cardiac transplant recipients at risk of rejection.
Identifiants
pubmed: 32185871
doi: 10.1111/ajt.15863
pmc: PMC7494540
mid: NIHMS1579187
pii: S1600-6135(22)22465-4
doi:
Substances chimiques
Antibodies
0
HLA Antigens
0
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2768-2780Subventions
Organisme : NIAID NIH HHS
ID : R01 AI135201
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI042819
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK104687-02
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.
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