Autoimmunity to vimentin is associated with outcomes of patients with idiopathic pulmonary fibrosis
Open accessAbstract
Autoimmunity has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF); however, the repertoire of autoantigens involved in this disease and the clinical relevance of these autoimmune responses are still being explored. Our initial discovery assays demonstrated that circulating and intrapulmonary vimentin levels are increased in IPF patients. Subsequent studies showed native vimentin induced HLA-DR–dependent in vitro proliferation of CD4 T cells from IPF patients and enhanced the production of IL-4, IL-17, and TGF-β1 by these lymphocytes in contrast to normal control specimens. Vimentin supplementation of IPF PBMC cultures also resulted in HLA-DR–dependent production of IgG with anti-vimentin specificities. Circulating anti-vimentin IgG autoantibody levels were much greater in IPF subjects from the University of Alabama at Birmingham (n = 102) and the University of Pittsburgh (U. Pitt., n = 70) than in normal controls. Anti-vimentin autoantibody levels in IPF patients were HLA biased and inversely correlated with physiological measurements of lung function (i.e., forced expiratory volumes and diffusing capacities). Despite considerable intergroup differences in transplant-free survival between these two independent IPF cohorts, serious adverse outcomes were most frequent among the patients within each population that had the highest anti-vimentin autoantibody levels (University of Alabama at Birmingham: hazard ratio 2.5, 95% confidence interval 1.2–5.3, p = 0.012; University of Pittsburgh: hazard ratio 2.7, 95% confidence interval 1.3–5.5, p = 0.006). These data show that anti-vimentin autoreactivity is prevalent in IPF patients and is strongly associated with disease manifestations. These findings have implications with regard to the pathogenesis of this enigmatic disease and raise the possibility that therapies specifically directed at these autoimmune processes could have therapeutic efficacy.
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High levels of anti-vimentin are associated with worsened pulmonary function and prognosis in IPF.
“high levels of anti-vimentin were associated with worsened pulmonary function and prognosis (165).”
From The Role of Immune and Inflammatory Cells in Idiopathic Pulmonary Fibrosis (2018) · cites this paper as [165]
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- Authors
- Li, F. J., Surolia, R., Li, H., Wang, Z., Kulkarni, T., Liu, G., de Andrade, J. A., Kass, D. J., Thannickal, V. J., Duncan, S. R., & Antony, V. B.
- Affiliations
- University of Alabama at Birmingham (US)
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham , Birmingham, AL 35294
- University of Pittsburgh (US)
- Corresponding author
- Surolia, Ranu
- Li, Huashi
- Wang, Zheng
- Kulkarni, Tejaswini
- Liu, Gang
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-09-01
- Volume
- 199
- Issue
- 5
- Pages
- 1596-1605
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC5563167
- OpenAlex
- W2740263004
- Cited by
- 85
- References
- 50
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 16 · 2022: 8 · 2021: 15 · 2020: 10 · 2019: 12 · 2018: 11 · 2017: 1
- FWCI
- 7.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (HL114470)
- National Institute on Aging (R01AG046210)
- National Heart, Lung, and Blood Institute (R01HL126990, R01HL119960, P01HL114470)
- 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 › Rheumatology › IgG4-Related and Inflammatory Diseases
- Keywords
- idiopathic pulmonary fibrosis, vimentin, autoimmunity, autoantigens, CD4+ T cell proliferation, HLA-DR, IL-17, IL-4, TGF-β1, lung function, transplant-free survival, disease outcome
- MeSH terms
- Alleles, Autoantibodies, Cells, Cultured, HLA-DR Antigens, Humans, Lung, Polymorphism, Genetic, Prospective Studies, Pulmonary Fibrosis, Vimentin, Cohort Studies, CD4-Positive T-Lymphocytes, Autoimmunity, Interleukin-4, Survival Analysis, Genetic Predisposition to Disease, Interleukin-17, Cell Proliferation, Transforming Growth Factor beta1, Patient Outcome Assessment
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