SYNOVIAL FLUID T CELL REACTIVITY AGAINST 65 kD HEAT SHOCK PROTEIN OF MYCOBACTERIA IN EARLY CHRONIC ARTHRITIS

Res, Pieter; Breedveld, F. C.; Embden, JanD.A. Van; Schaar, CeesG.; Eden, Willem van; Cohen, I.R.; Vries, RenéR.P. de

doi:10.1016/s0140-6736(88)90123-7

Cited by 277 publications

(124 citation statements)

References 9 publications

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“…Similar to our findings, T cell reactivity to hsp60 as measured by proliferation assays has been found in some, but not all, RA patients studied previously (7)(8)(9)(10). In contrast, increased expression of hsp60 or an immunologically crossreactive molecule in the inflamed synovium of rheumatoid joints has been demonstrated to be a feature in all patients (5).…”

Section: Resultssupporting

confidence: 90%

“…Using proliferation assays, T cell reactivity to mycobacterial hsp60 has been demonstrated at sites of chronic inflammation, including the synovial fluid (SF) of patients with RA or other arthropathies (7)(8)(9)(10). Recently, T cell proliferative responses against endogenous human hsp60 were observed in the SF of patients with early, nonerosive juvenile chronic arthritis.…”

Section: Cartilage Pg Synthesis This Suppression Is Mediated By Il-1mentioning

confidence: 99%

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Suppression of human cartilage proteoglycan synthesis by rheumatoid synovial fluid mononuclear cells activated with mycobacterial 60‐kd heat‐shock protein

Wilbrink¹,

Holewijn²,

Bijlsma³

et al. 1993

Arthritis & Rheumatism

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Objective. To examine whether T cell reactivity toward heat-shock proteins (HSP) contributes to cartilage destruction in rheumatoid arthritis (RA).Methods. An in vitro system was used, in which human cartilage explants were cocultured with hsp60-activated synovial fluid mononuclear cells (SFMC) from patients with RA, and proteoglycan (PG) synthesis was measured.Results. The hsp60-activated SFMC suppressed cartilage PG synthesis. This effect was dependent on the production of interleukin-1 (IL-1) and tumor necrosis factor a (TNFa).Conclusion. Mycobacterial60-kd heat-shock protein can activate rheumatoid SFMC to suppress human From the

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Section: Resultssupporting

confidence: 90%

Section: Cartilage Pg Synthesis This Suppression Is Mediated By Il-1mentioning

confidence: 99%

Suppression of human cartilage proteoglycan synthesis by rheumatoid synovial fluid mononuclear cells activated with mycobacterial 60‐kd heat‐shock protein

Wilbrink¹,

Holewijn²,

Bijlsma³

et al. 1993

Arthritis & Rheumatism

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“…Our preliminary data (not presented), as well as recently published observations (30), suggest that the 65-kd protein may be the immunodominant antigen, within the AP-MT complex, for the activation of synovial fluid lymphocytes. The 65-kd protein appears to possess cross-reactive epitopes, with amino acid sequences partially homologous with those of hyaline cartilage proteins (15,3 1).…”

Section: Discussionsupporting

confidence: 70%

Antigenic specificity of rheumatoid synovial fluid lymphocytes

Pope

Pahlavani

LaCour

et al. 1989

Arthritis & Rheumatism

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The majority of rheumatoid arthritis (RA) synovial fluid lymphocytes (SFL) demonstrate markers that are suggestive of prior activation. While the mechanism(s) responsible is unknown, prior studies have suggested that certain Mycobacterium tuberculosis (MT) antigens may preferentially activate SFL in vitro. We therefore examined the ability of RA SFL to respond to purified protein derivative and an acetone‐precipitable MT antigenic complex (AP‐MT) and compared this with the responses by peripheral blood lymphocytes (PBL). The responses were contrasted with those elicited with tetanus toxoid (TT) and mitogenic anti‐CD3. In patients with RA, the SF proliferative responses to both TT and anti‐CD3 were reduced compared with responses by PB. In contrast, the SF response to purified protein derivative was maintained, and that to AP‐MT was significantly increased, compared with PB. SF responses to AP‐MT antigens were significantly greater than those to TT. The AP‐MT activation of T lymphocytes from RA SF was characterized by an earlier peak proliferative response than that noted with matched PB. AP‐MT responsiveness was not restricted to HLA–DR4 positive patients. These observations suggest that an epitope(s) contained within the MT complex of antigens, and enriched in the AP‐MT complex, may be important in maintaining the chronic inflammation in at least some patients with RA.

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“…T cells and antibodies generated against microbial HSP may target self-HSP, either through the recognition of conserved epitopes or via cross-reactivity (molecular mimicry), thus leading to tissue inflammation (111,112). The responses induced by molecular mimicry between bacterial and mammalian Hsp60 and Hsp70 have been implicated in the pathogenesis of some autoimmune and inflammatory diseases, including type-1 diabetes (113), atherosclerosis (114), arthritis (115) and MS (116)(117)(118)(119), and elevated levels of extracellular HSP and anti-self HSP antibodies have been found in patients with these diseases. However, contrary to expectations, in several studies using animal models of arthritis (120,121), diabetes and MS (122,123) as well as in clinical trials (124), preimmunization with bacterial gp96, Hsp60 or Hsp70 abrogated the subsequently induced inflammatory disease.…”

Section: Molecular Mimicrymentioning

confidence: 99%

Heat Shock Protein 70: Roles in Multiple Sclerosis

Mansilla

Montalbán

Espejo

2012

Mol Med

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Heat shock proteins (HSP) have long been considered intracellular chaperones that possess housekeeping and cytoprotective functions. Consequently, HSP overexpression was proposed as a potential therapy for neurodegenerative diseases characterized by the accumulation or aggregation of abnormal proteins. Recently, the discovery that cells release HSP with the capacity to trigger proinflammatory as well as immunoregulatory responses has focused attention on investigating the role of HSP in chronic inflammatory autoimmune diseases such as multiple sclerosis (MS). To date, the most relevant HSP is the inducible Hsp70, which exhibits both cytoprotectant and immunoregulatory functions. Several studies have presented contradictory evidence concerning the involvement of Hsp70 in MS or experimental autoimmune encephalomyelitis (EAE), the MS animal model. In this review, we dissect the functions of Hsp70 and discuss the controversial data concerning the role of Hsp70 in MS and EAE.

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SYNOVIAL FLUID T CELL REACTIVITY AGAINST 65 kD HEAT SHOCK PROTEIN OF MYCOBACTERIA IN EARLY CHRONIC ARTHRITIS

Cited by 277 publications

References 9 publications

Suppression of human cartilage proteoglycan synthesis by rheumatoid synovial fluid mononuclear cells activated with mycobacterial 60‐kd heat‐shock protein

Suppression of human cartilage proteoglycan synthesis by rheumatoid synovial fluid mononuclear cells activated with mycobacterial 60‐kd heat‐shock protein

Antigenic specificity of rheumatoid synovial fluid lymphocytes

Heat Shock Protein 70: Roles in Multiple Sclerosis

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