Cerebrospinal fluids containing anti-HSP70 autoantibodies from multiple sclerosis patients augment HSP70-induced proinflammatory cytokine production in monocytic cells

Yokota, Shinichi; Chiba, Susumu; Furuyama, Hiroyasu; Fujii, Nobuhiro

doi:10.1016/j.jneuroim.2009.10.009

Cited by 23 publications

(14 citation statements)

References 21 publications

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“…The present data, in conjunction with other independent evidences in IPF patients (4-22), illuminate several parallels between this lung disease and recognized autoimmune syndromes (34-39,41,42,46,49). Thus, these collective findings may be an impetus to consider innovative experimental trials for this inexorable and highly lethal syndrome.…”

Section: Discussionsupporting

confidence: 86%

“…Autoantibodies can also deleteriously alter target cell functions (13,16,42,43) by cross-linking cell surface autoantigen-receptor complexes that transduce and enhance proinflammatory responses, or after gaining access to intracellular autoantigens (44). Previous studies have shown that autoantibodies of IPF patients increase the production of pro-fibrotic TGF-P by alveolar epithelia (16).…”

Section: Discussionmentioning

confidence: 99%

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Plasma B Lymphocyte Stimulator and B Cell Differentiation in Idiopathic Pulmonary Fibrosis Patients

Xue

Kass

Bon

et al. 2013

The Journal of Immunology

152

130

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We hypothesized B-cells are involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF), a progressive, restrictive lung disease that is refractory to glucocorticoids and other nonspecific therapies, and almost invariably lethal. Accordingly, we sought to identify clinically-associated B-cell-related abnormalities in these patients. Phenotypes of circulating B-cells were characterized by flow cytometry. Intrapulmonary processes were evaluated by immunohistochemistry. Plasma B-lymphocyte stimulating factor (BLyS) was assayed by ELISA. Circulating B-cells of IPF subjects were more antigen-differentiated, with greater plasmablast proportions (3.1±0.8%) than in normal controls (1.3±0.3%) (p<0.03), and the extent of this differentiation correlated with IPF patient lung volumes (r=0.44, p<0.03). CD20+ B-cell aggregates, diffuse parenchymal and perivascular immune complexes, and complement depositions were all prevalent in IPF lungs, but much less prominent or absent in normal lungs. Plasma concentrations of BLyS, an obligate factor for B-cell survival and differentiation, were significantly greater (p<0.0001) in 110 IPF (2.05±0.05 ng/ml) than among 53 normal (1.40±0.04 ng/ml) and 90 chronic obstructive pulmonary disease (COPD) subjects (1.59±0.05 ng/ml). BLyS levels were uniquely correlated among IPF patients with pulmonary artery pressures (r=0.58, p<0.0001). The 25% of IPF subjects with the greatest BLyS values also had diminished one-year survival (46±11%), compared to those with lesser BLyS concentrations (81±5%) (HR=4.0, 95%CI=1.8-8.7, p=0.0002). Abnormalities of B-cells and BLyS are common in IPF patients, and highly associated with disease manifestations and patient outcomes. These findings have implications regarding IPF pathogenesis, and illuminate the potential for novel treatment regimens that specifically target B-cells in patients with this lung disease.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Plasma B Lymphocyte Stimulator and B Cell Differentiation in Idiopathic Pulmonary Fibrosis Patients

Xue

Kass

Bon

et al. 2013

The Journal of Immunology

152

130

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“…Multiple sclerosis (MS) is a chronic inflammatory CNS disease of autoimmune etiology, caused by an inappropriate immune T-cell-mediated response to CNS myelin antigens [213, 214]. In this disease, myelin antigens such as myelin basic protein (MBP), one of the most immunogenic proteins of the CNS and synthesized in the CNS only by oligodendrocytes, proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG), myelin-associated glycoprotein, and nonmyelin antigens such as αβ -crystallin, transaldolase, and CNPase, are believed to be targets of pathogenic T cells [215–222].…”

Section: Hsp70 and Immunomodulation: A Negative Role In Autoimmunementioning

confidence: 99%

Hsp70 and Its Molecular Role in Nervous System Diseases

Turturici

Sconzo

Geraci

2011

Biochemistry Research International

200

154

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Heat shock proteins (HSPs) are induced in response to many injuries including stroke, neurodegenerative disease, epilepsy, and trauma. The overexpression of one HSP in particular, Hsp70, serves a protective role in several different models of nervous system injury, but has also been linked to a deleterious role in some diseases. Hsp70 functions as a chaperone and protects neurons from protein aggregation and toxicity (Parkinson disease, Alzheimer disease, polyglutamine diseases, and amyotrophic lateral sclerosis), protects cells from apoptosis (Parkinson disease), is a stress marker (temporal lobe epilepsy), protects cells from inflammation (cerebral ischemic injury), has an adjuvant role in antigen presentation and is involved in the immune response in autoimmune disease (multiple sclerosis). The worldwide incidence of neurodegenerative diseases is high. As neurodegenerative diseases disproportionately affect older individuals, disease-related morbidity has increased along with the general increase in longevity. An understanding of the underlying mechanisms that lead to neurodegeneration is key to identifying methods of prevention and treatment. Investigators have observed protective effects of HSPs induced by preconditioning, overexpression, or drugs in a variety of models of brain disease. Experimental data suggest that manipulation of the cellular stress response may offer strategies to protect the brain during progression of neurodegenerative disease.

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“…Evaluation of extracellular hsp70 release in various other disease models implicates this protein as an important inflammatory mediator and contributor to tissue damage. Apparent mechanisms of action include interacting with Toll-like receptors (TLR), inducing pro-inflammatory cytokine expression via the NF-KB pathway, up-regulating macrophage-mediated phagocytosis, and enhancing apoptosis (Clemons and Anderson, 2006; Kovalchin et al, 2006; Yokota et al, 2010). …”

Section: Resultsmentioning

confidence: 99%

Involvement of the choroid plexus in the inflammatory response after acute spinal cord injury in dogs: An immunohistochemical study

Moore

Oglesbee

2012

Veterinary Immunology and Immunopathology

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The choroid plexus (CP) is increasingly recognized as an important contributor to central nervous system (CNS) inflammation by recruitment of inflammatory cells and release of inflammatory cytokines. Here we investigate the role of the CP epithelium (CPE) as a source of three pro-inflammatory molecules of potential importance in inflammation after acute spinal cord injury (SCI): IL-1β, TNF-α, and hsp70. Immunohistochemical (IHC) staining for these three proteins was performed on 4th ventricular CPE from 4 dogs euthanized 12–48 h after spontaneous acute SCI, and from 4 neurologically normal dogs euthanized for other reasons. IHC staining was quantified using Aperio ImageScope software. IHC staining in the CPE of dogs with acute SCI was 2.2, 1.6 and 1.5 times higher than that of normal dogs, for IL-1β, TNF-α, and hsp70, respectively. Increases were statistically significant (p < 0.1) for IL-1β and TNF-α, and closely approached significance for hsp70. These findings indicate that the CPE could serve as an important source of these inflammatory mediators after SCI. There was also an inverse correlation between IL-1β and hsp70 staining and duration of clinical signs in acute SCI, suggesting that increased expression of these proteins by the CPE may be of particular importance in the immediate-early inflammatory response after acute SCI.

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Cerebrospinal fluids containing anti-HSP70 autoantibodies from multiple sclerosis patients augment HSP70-induced proinflammatory cytokine production in monocytic cells

Cited by 23 publications

References 21 publications

Plasma B Lymphocyte Stimulator and B Cell Differentiation in Idiopathic Pulmonary Fibrosis Patients

Plasma B Lymphocyte Stimulator and B Cell Differentiation in Idiopathic Pulmonary Fibrosis Patients

Hsp70 and Its Molecular Role in Nervous System Diseases

Involvement of the choroid plexus in the inflammatory response after acute spinal cord injury in dogs: An immunohistochemical study

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