About: Autoreactivity to Glucose Regulated Protein 78 Links Emphysema and Osteoporosis in Smokers

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About: Autoreactivity to Glucose Regulated Protein 78 Links Emphysema and Osteoporosis in Smokers Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Autoreactivity to Glucose Regulated Protein 78 Links Emphysema and Osteoporosis in Smokers
Creator	Zhang, Yingze Bhargava, Arpit Bon, Jessica Burger, Mathew Chandra, Divay Csizmadia, Eva Kahloon, Rehan Otterbein, Leo Tan, Jiangning Xue, Jianmin Duncan, Steven Fuhrman, Carl Kass, Daniel Pershouse, Mark Pilewski, Joseph Roodman, G Sciurba, Frank
source	PMC
abstract	RATIONALE: Emphysema 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. OBJECTIVES: To discover an antigen-specific autoimmune response associated with both emphysema and osteoporosis among smokers. METHODS: Replicate 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 RESULTS: Circulating 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). CONCLUSIONS: Humoral 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.
has issue date	2014-09-12(xsd:dateTime)
bibo:doi	10.1371/journal.pone.0105066
bibo:pmid	25216103
has license	cc-by
sha1sum (hex)	1a8daad89d2701b4cf603e668f6aab1209b6237e
schema:url	https://doi.org/10.1371/journal.pone.0105066
resource representing a document's title	Autoreactivity to Glucose Regulated Protein 78 Links Emphysema and Osteoporosis in Smokers
has PubMed Central identifier	PMC4162538
has PubMed identifier	25216103
schema:publication	PLoS One
resource representing a document's body	covid:1a8daad89d2701b4cf603e668f6aab1209b6237e#body_text
is schema:about of	named entity 'Glucose' covid:arg/1a8daad89d2701b4cf603e668f6aab1209b6237e named entity 'DISEASES' named entity 'OSTEOPOROSIS' named entity 'DISORDERS' named entity 'AUTOIMMUNE RESPONSES' named entity 'INVOLVED' named entity 'CIGARETTE SMOKERS' named entity 'UNKNOWN' named entity 'MECHANISM' named entity 'GLUCOSE' named entity 'REGULATED' named entity 'PROTEIN ' named entity 'OSTEOPOROSIS' named entity 'EMPHYSEMA' named entity 'LINKING' named entity 'THESE' named entity 'MAY BE' named entity 'RATIONALE' named entity 'EMPHYSEMA' named entity '28S' named entity 'ILLNESSES' named entity 'SMOKERS' named entity 'LINKS' named entity 'ASSOCIATED' named entity 'responses' named entity 'cigarette smokers' named entity 'illnesses' named entity 'hypothesized' named entity 'involved' named entity 'Protein' named entity 'epidemiologically' named entity 'autoimmune responses' named entity 'Osteoporosis' named entity 'Smokers' named entity 'IHC' named entity 'autoantibodies' named entity 'immunostaining' named entity 'false positive' named entity 'Applied Biosystems' named entity 'T-cells' named entity 'organ' named entity 'autoantigen' named entity 'polyacrylamide gel electrophoresis' named entity 'bone marrow' named entity 'lung disease' named entity 'lungs' named entity 'Rehovot' named entity 'autoantibody' named entity 'tobacco smoking' named entity 'emphysema' named entity 'Roche' named entity 'plasma' named entity 'positive or negative' named entity 'tissue injury' named entity 'autoantibody' named entity 'CCL-2' named entity 'osteoporosis' named entity 'pro-inflammatory' named entity 'autoimmune responses' named entity 'GRP78' named entity 'biological plausibility' named entity 'anti-inflammatory' named entity 'GRP78' named entity 'bone demineralization'

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