Anti-type V collagen humoral immunity in lung transplant primary graft dysfunction

Takekazu Iwata, Alexander Philipovskiy, Amanda J. Fisher, Robert G. Presson, Masako Chiyo, Jae Lee, Elizabeth Mickler, Gerald N. Smith, Irina Petrache, David B. Brand, William J. Burlingham, Bagavathi Gopalakrishnan, Daniel S. Greenspan, Jason D. Christie, David S. Wilkes

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

Primary graft dysfunction (PGD) is a major complication following lung transplantation. We reported that anti-type V collagen (col(V)) T cell immunity was strongly associated with PGD. However, the role of preformed anti-col(V) Abs and their potential target in PGD are unknown. Col(V) immune serum, purified IgG or B cells from col(V) immune rats were transferred to WKY rat lung isograft recipients followed by assessments of lung pathology, cytokines, and PaO 2/FiO2, an index of lung dysfunction in PGD. Immune serum, purified IgG, and B cells all induced pathology consistent with PGD within 4 days posttransfer; upregulated IFN-γ, TNF-α, and IL-1β locally; and induced significant reductions in PaO2/FiO2. Depleting anti-col(V) Abs before transfer demonstrated that IgG2c was a major subtype mediating injury. Confocal microscopy revealed strong apical col(V) expression on lung epithelial, but not endothelial cells; which was consistent with the ability of col(V) immune serum to induce complement-dependent cytotoxicity only in the epithelial cells. Examination of plasma from patients with or without PGD revealed that higher levels of preformed anti-col(V) Abs were strongly associated with PGD development. This study demonstrates a major role for anti-col(V) humoral immunity in PGD, and identifies the airway epithelium as a target in PGD.

Original languageEnglish (US)
Pages (from-to)5738-5747
Number of pages10
JournalJournal of Immunology
Volume181
Issue number8
DOIs
StatePublished - 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Iwata, T., Philipovskiy, A., Fisher, A. J., Presson, R. G., Chiyo, M., Lee, J., Mickler, E., Smith, G. N., Petrache, I., Brand, D. B., Burlingham, W. J., Gopalakrishnan, B., Greenspan, D. S., Christie, J. D., & Wilkes, D. S. (2008). Anti-type V collagen humoral immunity in lung transplant primary graft dysfunction. Journal of Immunology, 181(8), 5738-5747. https://doi.org/10.4049/jimmunol.181.8.5738