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

Transpl Immunol. 2019 Oct:56:101224. doi: 10.1016/j.trim.2019.101224. Epub 2019 Jul 17.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 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


  • Antigens, CD19
  • Collagen Type V