Association of humoral immunity and bronchiolitis obliterans syndrome.
Animal studies have shown that blockade of complement may reduce the severity of and/or prevent the development of bronchiolitis obliterans syndrome (BOS), suggesting a role for complement activation. We explored the hypothesis that humoral immunity plays a role in the evolution of BOS. Thirteen unilateral lung transplant patients with BOS defined the patient population. Fresh frozen tissue was analyzed for deposition of C1q, C4d, C5b-9 and immunoglobulin (IgG, IgM, IgA). An indirect immunofluorescent assay was also conducted with patient serum against cytospins of the pulmonary endothelium. In each case the biopsies showed a microvascular injury syndrome involving the bronchial wall characterized by one or more of hemorrhage, fibrin deposition, and endothelial cell necrosis. Other features included bronchial epithelial and chondrocyte necrosis. The end-stage lesion was a thinned bronchial epithelial lining mural fibrosis. Immunofluorescent analysis showed deposition of C1q, C3, C4d, C5b-9, and immunoglobulin in the bronchial epithelium, chondrocytes, basement membrane zone of the bronchial epithelium, and bronchial wall microvasculature. The indirect antiendothelial cell antibody assay was positive in all tested. Humoral immunity may play a role in the pathogenesis of BOS; the antigenic targets include the bronchial wall microvasculature, bronchial epithelium, and chondrocytes.
Magro
Cynthia M
CM
Department of Pathology, The Ohio State University, Columbus, OH, USA.
Ross
Patrick
P
Kelsey
Moira
M
Waldman
W James
WJ
Pope-Harman
Amy
A
D000368:Aged; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D001989:Bronchiolitis Obliterans / Q000276:immunology*; D003181:Complement C4 / Q000032:analysis; D015935:Complement C4b; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D016040:Lung Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis; D011183:Postoperative Complications / Q000276:immunology / Q000473:pathology
D015415:Biomarkers; D003181:Complement C4; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d