ArticlePloS one2014
Autoreactivity to glucose regulated protein 78 links emphysema and osteoporosis in smokers.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Autoantibodies in chronic non-infectious respiratory diseases: a scoping review.Frontiers in immunology · 2026Article
- Contribution of adaptive immunity to human COPD and experimental models of emphysema.Physiological reviews · 2023Review
- Endoplasmic Reticulum Stress in Chronic Obstructive Pulmonary Disease: Mechanisms and Future Perspectives.Biomolecules · 2022Review
- Set Up for Failure: Pre-Existing Autoantibodies in Lung Transplant.Frontiers in immunology · 2021Review
- Bisphosphonates Reduce Smoking-Induced Osteoporotic-Like Alterations by Regulating RANKL/OPG in an Osteoblast and Osteoclast Co-Culture Model.International journal of molecular sciences · 2020Article
- Dissociation between airway and systemic autoantibody responses in chronic obstructive pulmonary disease.Annals of translational medicine · 2020Article
- Endoplasmic reticulum stress and glutathione therapeutics in chronic lung diseases.Redox biology · 2020Review
- Glucose-Regulated Protein 78 Autoantibodies Are Associated with Carotid Atherosclerosis in Chronic Obstructive Pulmonary Disease Patients.ImmunoHorizons · 2020Article
- Loss of skin elasticity is associated with pulmonary emphysema, biomarkers of inflammation, and matrix metalloproteinase activity in smokers.Respiratory research · 2019Article
- A Phenome-Wide Association Study Uncovers a Role for Autoimmunity in the Development of Chronic Obstructive Pulmonary Disease.American journal of respiratory cell and molecular biology · 2018Article
- Is osteoporosis an autoimmune mediated disorder?Bone reports · 2017Review
- Secretion of the endoplasmic reticulum stress protein, GRP78, into the BALF is increased in cigarette smokers.Respiratory research · 2017Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
rationaleEmphysema and osteoporosis are epidemiologically associated diseases of cigarette smokers. The causal mechanism(s) linking these illnesses is unknown. We hypothesized autoimmune responses may be involved in both disorders.
objectivesTo discover an antigen-specific autoimmune response associated with both emphysema and osteoporosis among smokers.
methodsReplicate nonbiased discovery assays indicated that autoimmunity to glucose regulated protein 78 (GRP78), an endoplasmic reticulum chaperone and cell surface signaling receptor, is present in many smokers. Subject assessments included spirometry, chest CT scans, dual x-ray absorptiometry, and immunoblots for anti-GRP78 IgG. Anti-GRP78 autoantibodies were isolated from patient plasma by affinity chromatography, leukocyte functions assessed by flow cytometry, and soluble metabolites and mediators measured by immunoassays. MEASUREMENTS AND MAIN
resultsCirculating anti-GRP78 IgG autoantibodies were detected in plasma specimens from 86 (32%) of the 265 smoking subjects. Anti-GRP78 autoantibodies were singularly prevalent among subjects with radiographic emphysema (OR 3.1, 95%CI 1.7-5.7, p = 0.003). Anti-GRP78 autoantibodies were also associated with osteoporosis (OR 4.7, 95%CI 1.7-13.3, p = 0.002), and increased circulating bone metabolites (p = 0.006). Among emphysematous subjects, GRP78 protein was an autoantigen of CD4 T-cells, stimulating lymphocyte proliferation (p = 0.0002) and IFN-gamma production (p = 0.03). Patient-derived anti-GRP78 autoantibodies had avidities for osteoclasts and macrophages, and increased macrophage NFkB phosphorylation (p = 0.005) and productions of IL-8, CCL-2, and MMP9 (p = 0.005, 0.007, 0.03, respectively).
conclusionsHumoral and cellular GRP78 autoimmune responses in smokers have numerous biologically-relevant pro-inflammatory and other deleterious actions, and are associated with emphysema and osteoporosis. These findings may have relevance for the pathogenesis of smoking-associated diseases, and development of biomarker immunoassays and/or novel treatments for these disorders.
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