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

Full 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)/FiO(2), an index of lung dysfunction in PGD. Immune serum, purified IgG, and B cells all induced pathology consistent with PGD within 4 days posttransfer; up-regulated IFN-gamma, TNF-alpha, and IL-1beta locally; and induced significant reductions in PaO(2)/FiO(2). 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.

Author information

Author/s: Iwata, Takekazu (T); Philipovskiy, Alexander (A); Fisher, Amanda J (AJ); Presson, Robert G (RG); Chiyo, Masako (M); Lee, Jae (J); Mickler, Elizabeth (E); Smith, Gerald N (GN); Petrache, Irina (I); Brand, David B (DB); Burlingham, William J (WJ); Gopalakrishnan, Bagavathi (B); Greenspan, Daniel S (DS); Christie, Jason D (JD); Wilkes, David S (DS);

Affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Grants: AI048624 (Agency:NIAID NIH HHS) ; AI066219 (Agency:NIAID NIH HHS) ; AR53815 (Agency:NIAMS NIH HHS) ; GM71679 (Agency:NIGMS NIH HHS) ; HL 077328 (Agency:NHLBI NIH HHS) ; HL/AL67177 (Agency:NHLBI NIH HHS) ; HL081350 (Agency:NHLBI NIH HHS) ; HL081619 (Agency:NHLBI NIH HHS) ; HL087115 (Agency:NHLBI NIH HHS) ; HL60797 (Agency:NHLBI NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.

Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol), published in United States. (Language: eng)

Reference: 2008-Oct; vol 181 (issue 8) : pp 5738-47

Dates: Created 2008/10/03; Completed 2008/10/21;

PMID: 18832733, status: MEDLINE (last retrieved date: 2/18/2009)

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