Collagen type-V is a danger signal associated with primary graft dysfunction in lung transplantation.
Adult
Aged
Animals
Antibody Formation
Antigens, CD19
/ metabolism
B-Lymphocyte Subsets
/ physiology
Cells, Cultured
Collagen Type V
/ immunology
Female
Flow Cytometry
Graft Rejection
/ immunology
Humans
Immunity, Innate
Lung Transplantation
Lymphocyte Activation
/ genetics
Male
Mice
Mice, Inbred C57BL
Middle Aged
Transcriptome
Collagen type-V
Lung transplant
Primary graft dysfunction
Journal
Transplant immunology
ISSN: 1878-5492
Titre abrégé: Transpl Immunol
Pays: Netherlands
ID NLM: 9309923
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
12
04
2019
revised:
09
07
2019
accepted:
16
07
2019
pubmed:
22
7
2019
medline:
4
4
2020
entrez:
21
7
2019
Statut:
ppublish
Résumé
Primary graft dysfunction (PGD) is the leading cause of early mortality after lung transplantation. Anti-collagen type-V (col(V)) immunity has been observed in animal models of ischemia-reperfusion injury (IRI) and in PGD. We hypothesized that collagen type-V is an innate danger signal contributing to PGD pathogenesis. Anti-col(V) antibody production was detected by flow cytometric assay following cultures of murine CD19+ splenic cells with col.(V). Responding murine B cells were phenotyped using surface markers. RNA-Seq analysis was performed on murine CD19+ cells. Levels of anti-col(V) antibodies were measured in 188 recipients from the Lung Transplant Outcomes Group (LTOG) after transplantation. Col(V) induced rapid production of anti-col(V) antibodies from murine CD19+ B cells. Subtype analysis demonstrated innate B-1 B cells bound col.(V). Col(V) induced a specific transcriptional signature in CD19+ B cells with similarities to, yet distinct from, B cell receptor (BCR) stimulation. Rapid de novo production of anti-col(V) Abs was associated with an increased incidence of clinical PGD after lung transplant. This study demonstrated that col.(V) is an rapidly recognized by B cells and has specific transcriptional signature. In lung transplants recipients the rapid seroconversion to anti-col(V) Ab is linked to increased risk of grade 3 PGD.
Sections du résumé
BACKGROUND
Primary graft dysfunction (PGD) is the leading cause of early mortality after lung transplantation. Anti-collagen type-V (col(V)) immunity has been observed in animal models of ischemia-reperfusion injury (IRI) and in PGD. We hypothesized that collagen type-V is an innate danger signal contributing to PGD pathogenesis.
METHODS
Anti-col(V) antibody production was detected by flow cytometric assay following cultures of murine CD19+ splenic cells with col.(V). Responding murine B cells were phenotyped using surface markers. RNA-Seq analysis was performed on murine CD19+ cells. Levels of anti-col(V) antibodies were measured in 188 recipients from the Lung Transplant Outcomes Group (LTOG) after transplantation.
RESULTS
Col(V) induced rapid production of anti-col(V) antibodies from murine CD19+ B cells. Subtype analysis demonstrated innate B-1 B cells bound col.(V). Col(V) induced a specific transcriptional signature in CD19+ B cells with similarities to, yet distinct from, B cell receptor (BCR) stimulation. Rapid de novo production of anti-col(V) Abs was associated with an increased incidence of clinical PGD after lung transplant.
CONCLUSIONS
This study demonstrated that col.(V) is an rapidly recognized by B cells and has specific transcriptional signature. In lung transplants recipients the rapid seroconversion to anti-col(V) Ab is linked to increased risk of grade 3 PGD.
Identifiants
pubmed: 31325493
pii: S0966-3274(19)30045-0
doi: 10.1016/j.trim.2019.101224
pii:
doi:
Substances chimiques
Antigens, CD19
0
Collagen Type V
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
101224Subventions
Organisme : NHLBI NIH HHS
ID : T32 HL091816
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI084853
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL087115
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL096845
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.