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

Publication ,  Journal Article
Zaffiri, L; Shah, RJ; Stearman, RS; Rothhaar, K; Emtiazjoo, AM; Yoshimoto, M; Fisher, AJ; Mickler, EA; Gartenhaus, MD; Cohort, LTOG; Geraci, MW ...
Published in: Transpl Immunol
October 2019

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.

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Published In

Transpl Immunol

DOI

EISSN

1878-5492

Publication Date

October 2019

Volume

56

Start / End Page

101224

Location

Netherlands

Related Subject Headings

  • Transcriptome
  • Surgery
  • Middle Aged
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Lymphocyte Activation
  • Lung Transplantation
  • Immunity, Innate
  • Humans
 

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MLA
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Zaffiri, L., Shah, R. J., Stearman, R. S., Rothhaar, K., Emtiazjoo, A. M., Yoshimoto, M., … Wilkes, D. S. (2019). Collagen type-V is a danger signal associated with primary graft dysfunction in lung transplantation. Transpl Immunol, 56, 101224. https://doi.org/10.1016/j.trim.2019.101224
Zaffiri, Lorenzo, Rupal J. Shah, Robert S. Stearman, Katia Rothhaar, Amir M. Emtiazjoo, Momoko Yoshimoto, Amanda J. Fisher, et al. “Collagen type-V is a danger signal associated with primary graft dysfunction in lung transplantation.Transpl Immunol 56 (October 2019): 101224. https://doi.org/10.1016/j.trim.2019.101224.
Zaffiri L, Shah RJ, Stearman RS, Rothhaar K, Emtiazjoo AM, Yoshimoto M, et al. Collagen type-V is a danger signal associated with primary graft dysfunction in lung transplantation. Transpl Immunol. 2019 Oct;56:101224.
Zaffiri, Lorenzo, et al. “Collagen type-V is a danger signal associated with primary graft dysfunction in lung transplantation.Transpl Immunol, vol. 56, Oct. 2019, p. 101224. Pubmed, doi:10.1016/j.trim.2019.101224.
Zaffiri L, Shah RJ, Stearman RS, Rothhaar K, Emtiazjoo AM, Yoshimoto M, Fisher AJ, Mickler EA, Gartenhaus MD, Cohort LTOG, Diamond JM, Geraci MW, Christie JD, Wilkes DS. Collagen type-V is a danger signal associated with primary graft dysfunction in lung transplantation. Transpl Immunol. 2019 Oct;56:101224.
Journal cover image

Published In

Transpl Immunol

DOI

EISSN

1878-5492

Publication Date

October 2019

Volume

56

Start / End Page

101224

Location

Netherlands

Related Subject Headings

  • Transcriptome
  • Surgery
  • Middle Aged
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Lymphocyte Activation
  • Lung Transplantation
  • Immunity, Innate
  • Humans