| Identification of periplakin as a new target for autoreactivity in idiopathic pulmonary fibrosis. | |
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MedLine Citation:
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PMID: 20935114 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Rationale: Injury to alveolar epithelial cells is central to the pathophysiology of idiopathic pulmonary fibrosis (IPF). An abnormal autoimmune response directed against antigens of the alveolar epithelium may contribute to the disease. Objectives: To detect circulating autoantibodies (autoAbs) directed against epithelial structures. Methods: We performed immunoblot by separating human placental amnion extract or alveolar epithelial cell (A549 cell line) proteins on polyacrylamide gels, blotting on nitrocellulose membranes, and incubating with serum from patients with IPF (n = 40) or healthy subjects (n = 40). Proteomic analysis and mass spectrometry characterized the target protein. Inhibition experiments performed with the correspondent recombinant protein confirmed our results. Measurements and Main Results: We identified IgG autoAbs recognizing a 200-kD protein in the serum of patients with IPF. Proteomic analysis identified this protein as human periplakin (PPL), a component of desmosomes. Anti-PPL Abs were found by immunoblot in both serum and bronchoalveolar lavage in patients with IPF: 16/40 (40%) of them were positive versus none of the control subjects. Immunohistochemistry revealed that PPL was strongly expressed in bronchial and alveolar epithelium, but that PPL exhibited changes in intracellular localization among normal and fibrotic alveolar epithelium. In an alveolar epithelial wound repair assay, an anti-PPL IgG decreased cell migration. Recombinant PPL induced bronchoalveolar lavage T lymphocyte proliferation. Patients with IPF with anti-PPL Abs had a more severe respiratory disease, despite no difference in survival. Conclusions: We found a new circulating autoAb directed against PPL in patients with IPF, associated with a more severe disease. |
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Authors:
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Camille Taillé; Sabine Grootenboer-Mignot; Céline Boursier; Laurence Michel; Marie-Pierre Debray; Jérôme Fagart; Lorena Barrientos; Arnaud Mailleux; Natacha Cigna; Florence Tubach; Joëlle Marchal-Sommé; Paul Soler; Sylvie Chollet-Martin; Bruno Crestani |
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Publication Detail:
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Type: Journal Article Date: 2010-10-08 |
Journal Detail:
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Title: American journal of respiratory and critical care medicine Volume: 183 ISSN: 1535-4970 ISO Abbreviation: Am. J. Respir. Crit. Care Med. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-04-07 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421642 Medline TA: Am J Respir Crit Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 759-66 Citation Subset: AIM; IM |
Affiliation:
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Service de Pneumologie A, Hôpital Bichat, 46 rue Henri Huchard, 75877 Paris cedex 18, France. bruno.crestani@bch.aphp.fr. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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