Activation of human airway epithelial cells by non-HLA antibodies developed after lung transplantation: A potential etiological factor for bronchiolitis obliterans syndrome

Andres Jaramillo, Bashoo Naziruddin, Leiying Zhang, Scott I. Reznik, Michael A. Smith, Aviva A. Aloush, Elbert P. Trulock, G. Alexander Patterson, T. Mohanakumar

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Background. The main cause of morbidity and mortality after lung transplantation (LT) is bronchiolitis obliterans syndrome (BOS). Anti-HLA antibodies development after LT has been shown to play an important role in BOS pathogenesis. However, the nature of non-HLA antibodies developed after LT and their role in BOS pathogenesis have not been determined. Methods. Sera from 16 BOS+ patients and 11 BOS-patients were collected at 12, 24, 36, and 48 months after LT. Anti-HLA class I and class II antibodies were absorbed with pooled human platelets and pooled human lymphoblastoid cell lines, respectively. Then, the presence of non-HLA antibodies against several cell lines from different origin was determined by flow cytometric analysis. Antibody-positive samples were tested for induction of proliferation and growth factor production in two selected airway epithelial cell (AEC) lines. Results. Five of 16 BOS+ patients (31.2%) and 0 of 11 BOS- patients (0%) developed anti-AEC antibodies after LT (P=0.05). No reactivity against endothelial cells, lymphocytes, monocytes, or granulocytes was detected. Further analysis of two selected sera demonstrated the development of reactivity against a 60-kDa antigen expressed by 60% of AEC lines and only 12% of cell lines from other tissues. Antibody binding to this antigen induced intracellular Ca++ influx, tyrosine phosphorylation, proliferation, and up-regulation of transforming growth factor-β and heparin-binding epidermal growth factor mRNA transcription in AECs. Conclusions. These results indicate that anti-AEC antibodies may play a role in the immunopathogenesis of BOS in the absence of anti-HLA antibodies.

Original languageEnglish (US)
Pages (from-to)966-976
Number of pages11
JournalTransplantation
Volume71
Issue number7
DOIs
StatePublished - Apr 15 2001

ASJC Scopus subject areas

  • Transplantation

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