Collagen type-V is a danger signal associated with primary graft dysfunction in lung transplantation.
Journal Article (Journal Article)
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.
- 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
- October 2019
Volume / Issue
- 56 /
Start / End Page
- 101224 -
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)