Collagen type-V is a danger signal associated with primary graft dysfunction in lung transplantation

Lorenzo Zaffiri, Rupal J. Shah, Robert Stearman, K. Rothhaar, Amir M. Emtiazjoo, Momoko Yoshimoto, Amanda J. Fisher, Elizabeth A. Mickler, Matthew D. Gartenhaus, L. T.O.G. Cohort, Joshua M. Diamond, Mark W. Geraci, Jason D. Christie, David S. Wilkes

Research output: Contribution to journalArticle

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 languageEnglish (US)
Article number101224
JournalTransplant Immunology
Volume56
DOIs
StatePublished - Oct 1 2019

Fingerprint

Primary Graft Dysfunction
Collagen Type V
Lung Transplantation
B-Lymphocytes
Lung
Antibodies
Reperfusion Injury
Antibody Formation
Immunity
Animal Models
Transplantation
RNA
Transplants
Mortality

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 journalArticle

Zaffiri, L, Shah, RJ, Stearman, R, Rothhaar, K, Emtiazjoo, AM, Yoshimoto, M, Fisher, AJ, Mickler, EA, Gartenhaus, MD, Cohort, LTOG, Diamond, JM, Geraci, MW, Christie, JD & Wilkes, DS 2019, 'Collagen type-V is a danger signal associated with primary graft dysfunction in lung transplantation', Transplant Immunology, vol. 56, 101224. https://doi.org/10.1016/j.trim.2019.101224
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. / Collagen type-V is a danger signal associated with primary graft dysfunction in lung transplantation. In: Transplant Immunology. 2019 ; Vol. 56.
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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.",
keywords = "Collagen type-V, Lung transplant, Primary graft dysfunction",
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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

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