Anti-type V collagen humoral immunity in lung transplant primary graft dysfunction.
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.
Iwata
Takekazu
T
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
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
D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D002417:Cattle; D024062:Collagen Type V / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D042783:Endothelial Cells; D005786:Gene Expression Regulation / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000473:pathology; D016040:Lung Transplantation / Q000473:pathology; D051381:Rats; D011921:Rats, Inbred WKY; D014185:Transplantation, Isogeneic
D001323:Autoantibodies; D024062:Collagen Type V; D016207:Cytokines; D007074:Immunoglobulin G