Abstract
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.
| Original language | English (US) |
|---|---|
| Article number | 101224 |
| Journal | Transplant Immunology |
| Volume | 56 |
| DOIs | |
| State | Published - Oct 1 2019 |
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Keywords
- Collagen type-V
- Lung transplant
- Primary graft dysfunction
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Transplantation
Cite this
Collagen type-V is a danger signal associated with primary graft dysfunction in lung transplantation. / Zaffiri, Lorenzo; Shah, Rupal J.; Stearman, Robert; Rothhaar, K.; Emtiazjoo, Amir M.; Yoshimoto, Momoko; Fisher, Amanda J.; Mickler, Elizabeth A.; Gartenhaus, Matthew D.; Cohort, L. T.O.G.; Diamond, Joshua M.; Geraci, Mark W.; Christie, Jason D.; Wilkes, David S.
In: Transplant Immunology, Vol. 56, 101224, 01.10.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Collagen type-V is a danger signal associated with primary graft dysfunction in lung transplantation
AU - Zaffiri, Lorenzo
AU - Shah, Rupal J.
AU - Stearman, Robert
AU - Rothhaar, K.
AU - Emtiazjoo, Amir M.
AU - Yoshimoto, Momoko
AU - Fisher, Amanda J.
AU - Mickler, Elizabeth A.
AU - Gartenhaus, Matthew D.
AU - Cohort, L. T.O.G.
AU - Diamond, Joshua M.
AU - Geraci, Mark W.
AU - Christie, Jason D.
AU - Wilkes, David S.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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.
KW - Collagen type-V
KW - Lung transplant
KW - Primary graft dysfunction
UR - http://www.scopus.com/inward/record.url?scp=85070500788&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85070500788&partnerID=8YFLogxK
U2 - 10.1016/j.trim.2019.101224
DO - 10.1016/j.trim.2019.101224
M3 - Article
C2 - 31325493
AN - SCOPUS:85070500788
VL - 56
JO - Transplant Immunology
JF - Transplant Immunology
SN - 0966-3274
M1 - 101224
ER -