Circulating antibodies to lung protein(s) in patients with cryptogenic fibrosing alveolitis
Open accessAbstract
BACKGROUND: It has been hypothesised that cryptogenic fibrosing alveolitis has an immunological pathogenesis mediated by T lymphocytes. It is, however, recognised that patients may show dysregulation of the humoral immune system and that the presence of large numbers of B lymphocytes in open lung biopsies may be associated with a poor prognosis. Evidence of a role for the humoral immune system in the pathogenesis of cryptogenic fibrosing alveolitis has been suggested, but attempts to demonstrate circulating immunoglobulin to antigen within the lung have been inconclusive. METHODS: Plasma samples from 22 patients with cryptogenic fibrosing alveolitis, 22 patients with sarcoidosis, and 17 healthy controls were screened by SDS-PAGE and Western blotting for the presence of autoantibodies to lung proteins derived from cryptogenic fibrosing alveolitis, sarcoid and control lung tissue, as well as four normal non-pulmonary tissues. Possible site(s) of target protein(s) within the lung tissue were identified by immunohistochemical examination using IgG purified from the plasma of six patients and two controls. RESULTS: Eighteen of the plasma samples from patients with cryptogenic fibrosing alveolitis had reactive IgG to lung protein(s) in the 70-90 kDa molecular weight range compared with five of 18 plasma samples from patients with sarcoidosis and one of 17 controls. Plasma from patients with cryptogenic fibrosing alveolitis recognised antigen(s) of the same molecular weight in control and sarcoid lung tissue, but not non-pulmonary tissues, with a similar frequency. Immunohistochemical staining of cryptogenic fibrosing alveolitis biopsy material using IgG purified from plasma samples from patients with cryptogenic fibrosing alveolitis, but not control samples, revealed fine linear positivity in the lung parenchyma in a pattern suggestive of reaction with alveolar lining cells. The pattern was cytoplasmic/membranous and not nuclear. CONCLUSIONS: Patients with cryptogenic fibrosing alveolitis have a high frequency of plasma IgG autoantibodies to protein(s) within lung tissue associated with alveolar lining cells. This is believed to be the site where immunological injury occurs in cryptogenic fibrosing alveolitis, but the significance of these antibodies to the aetiology and pathogenesis is as yet unclear.
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A variety of novel autoantibodies targeting neoepitopes have been reported in IPF, with many targets being structural cell proteins such as desmoplakin and periplakin.
“A variety of novel autoantibodies targeting neoepitopes have been reported in IPF (159–163), with many of the targets being structural cell proteins, such as desmoplakin (164) and periplakin (159).”
From The Role of Immune and Inflammatory Cells in Idiopathic Pulmonary Fibrosis (2018) · cites this paper as [161]
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- Authors
- Wallace, W. A., Roberts, S. N., Caldwell, H., Thornton, E., Greening, A. P., Lamb, D., & Howie, S. E.
- Affiliations
- University of Edinburgh (GB)
- Venue
- Thorax
- Publisher
- BMJ
- Published
- 1994-03-01
- Volume
- 49
- Issue
- 3
- Pages
- 218-224
- ISSN
- 0040-6376 (ISSN-L)
- PMC
- PMC1021149
- OpenAlex
- W2127152031
- Cited by
- 52
- References
- 30
- Citations by year
- 2023: 2 · 2022: 1 · 2021: 3 · 2019: 1 · 2018: 4 · 2017: 1 · 2013: 1 · 2012: 3
- FWCI
- 2.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Thorax (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- British Lung Foundation
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
- Health Sciences › Medicine › Physiology › Sarcoidosis and Beryllium Toxicity Research
- Keywords
- idiopathic pulmonary fibrosis, autoantibodies, lung proteins, humoral immune response, sarcoidosis, autoantigens, immunopathogenesis, plasma IgG
- MeSH terms
- Aged, Autoantibodies, Electrophoresis, Polyacrylamide Gel, Female, Humans, Immunoglobulin G, Immunohistochemistry, Lung, Male, Proteins, Pulmonary Fibrosis, Blotting, Western
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