Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adjuvant arthritis (AA) can be induced in Lewis rats by immunization with mycobacterial antigens. Passive transfer of a T cell clone recognizing the 180-188 amino acid sequence in mycobacterial heat shock protein 60 (hsp60) was found to induce AA. In the present study, we investigated whether tolerance was obtained for this AA-associated T cell epitope after intranasal or s.c. administration of a peptide containing this epitope. Two 15-mer peptides containing the mycobacterial hsp60 sequences 176-190 and 211-225 were used; 176-190 contained the T cell epitope 180-188, which was recognized by the arthritogenic T cell clone A2b and was the immunodominant hsp60 T cell epitope after induction of AA, and 211-225 contained a T cell epitope that was recognized both after induction of arthritis with whole Mycobacterium tuberculosis and after immunization with mycobacterial hsp60. In rats treated intranasally or subcutaneously with 176-190 and immunized with mycobacterial hsp60, proliferative responses to 176-190 were reduced. Proliferative responses to 211-225 and to whole mycobacterial hsp60 were not affected. AA was inhibited intranasally in the 176-190-treated rats but not in the 211-225-treated rats. Moreover, intranasal 176-190 led to similar arthritis-protective effects in a nonmicrobially induced experimental arthritis (avridine-induced arthritis). Therefore, tolerance for a disease-triggering, microbial cartilage-mimicking epitope may cause resistance to arthritis irrespective of the actual trigger leading to development of the disease.
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PMID:Peptide-induced nasal tolerance for a mycobacterial heat shock protein 60 T cell epitope in rats suppresses both adjuvant arthritis and nonmicrobially induced experimental arthritis. 909 85

Sera from patients with sexually acquired reactive arthritis (SARA) with antibodies reacting with C. trachomatis and C. pneumoniae (group 1; n = 20) and also with C. psittaci (group 2; n = 19) were analyzed for antibody specificity. Sera from group 2 reacted significantly more often with C. trachomatis serotype E, H and K and had higher antibody titers to serotype E, as tested by microimmunofluorescence tests. Cross-reactivities occurring in microimmunofluorescence tests were related to the presence of antichlamydial lipopolysaccharide antibodies, adsorption of which by recombinant lipopolysaccharide removed microimmunofluorescence reactivity with C. psittaci antigen. In group 2, significantly more sera had antibodies to C. pneumoniae, remaining after lipopolysaccharide adsorption, as proved by adsorption with viable C. trachomatis and C. pneumoniae organisms. None of the sera had antibodies to Yersinia enterocolitica, Shigella flexneri, Sh. sonnei and Salmonella spp. It was observed that the frequency and titer of cross-reacting antibodies to chlamydial serotypes and species were related to the time period between the diagnosis of genital chlamydial infection and of SARA. Cross-reactivities were also related to the presence of lipopolysaccharide, but not heat shock protein 60- or neutralizing antibodies to chlamydiae. Antibody reactivity induced by antichlamydial lipopolysaccharide antibodies can be removed by lipopolysaccharide adsorption.
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PMID:Characterization of serum antibody response to chlamydiae in patients with sexually acquired reactive arthritis. 945 89

Adjuvant Arthritis (AA) can be induced in Lewis rats by immunisation with mycobacterial antigens. The disease can be passively transferred with T cell clone A2b, which recognises the 180-188 amino acid sequence in mycobacterial heat shock protein 60 (hsp60) and which crossreacts with crude cartilage proteoglycans. We succeeded to induce peripheral tolerance to this AA-associated T cell epitope following nasal administration of a peptide containing this epitope (mycobacterial hsp60 176-190). In rats treated nasally with 176-190 and immunised with mycobacterial hsp60, proliferative responses to 176-190 were reduced. AA was inhibited nasally with 176-190 treated rats and not in rats nasally treated with a control mycobacterial hsp60 peptide (211-225). Moreover, nasal 176-190 led to similar arthritis protective effects in a non-microbially induced experimental arthritis (avridine induced arthritis). In a subsequent study we tried to prevent and to treat AA through nasal administration of mycobacterial hsp60 peptide 180-188 and a peptide analogue of 180-188, 180-188(L183->A) (Alanine 183), which has been shown to have an increased MHC-binding affinity for rat RT1 Bl and an increased capacity to inhibit the proliferative A2b response in vitro. We found that nasal administration of 180-188 had a moderate arthritis suppressive effect in AA, whereas its analogue peptide Alanine 183, had a strong suppressive effect. This strong arthritis suppressive effect was only partly due to the higher MHC-binding affinity for rat RT1 Bl. Furthermore, it was possible to passively transfer nasal Alanine 183 induced disease protection. The present findings may in our view offer novel prospects for immunotherapy through nasal administration of (analogue) peptides, with a mimicry relationship with joint specific cartilage proteoglycan epitopes.
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PMID:Nasal administration of arthritis-related T cell epitopes of heat shock protein 60 as a promising way for immunotherapy in chronic arthritis. 955 75

1. Arthritis can be induced in rodents by priming T-cells to respond to a foreign antigen and then challenging with antigen intra-articularly. This may be a model of the situation in human reactive arthritis in which T-cell responses are induced by antigens from organisms which trigger reactive arthritis (e.g. Chlamydia trachomatis) and antigen finds its way to the joint, most probably within macrophages. Priming by previous exposure to antigens similar to those of the triggering organism could also play a part in pathogenesis. Genetic factors determining the nature and control of the immune response affect the severity and duration of the arthritis. 2. T-cell-dependent arthritis can be induced in rodents by immunization with an antigen known to be expressed in the joint (e.g. Type II collagen). Whether this is an important mechanism in human arthritis is still unclear, even though diseases such as rheumatoid arthritis are conventionally thought of as 'autoimmune'. No convincing candidate autoantigen has yet been identified in rheumatoid arthritis, and recent experiments in transgenic mice indicate that arthritis can be induced by an autoimmune T-cell response which does not target an antigen confined to the joint. 3. Adjuvant arthritis is a classical T-cell-dependent animal model of human arthritis; recently arthritis has been described as a rare complication in patients receiving adjuvant (intra-vesical live BCG organisms) for bladder cancer. Increasing attention is being paid to the role of adjuvants as 'danger signals', which allow the immune system to determine whether an antigenic challenge poses a threat. Inappropriate attachment of danger signals to self antigens may result in T-cell-mediated immune responses, which could play a part in the pathogenesis of arthritis. 4. Animal studies indicate that autoimmune/inflammatory diseases can be produced by imbalances within T-cell populations, and that certain T-cells also have the capacity to regulate inflammatory responses. Among the latter are T-cells specific for conserved epitopes within heat shock protein 60. The extent to which T-cells of this kind operate in human disease has yet to be determined.
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PMID:Role of T-cells in the development of arthritis. 966 82

The development of many autoimmune diseases has been etiologically linked to exposure to infectious agents. For example, a subset of patients with a history of Salmonella infection develop reactive arthritis. The persistence of bacterial antigen in arthritic tissue and the isolation of Salmonella or Yersinia reactive CD8+ T cells from the joints of patients with reactive arthritis support the etiological link between Gram-negative bacterial infection and autoimmune disease. Models proposed to account for the link between infection and autoimmunity include inflammation-induced presentation of cryptic self-epitopes, antigen persistence and molecular mimicry. Several studies support molecular mimicry as a mechanism for the involvement of class II epitopes in infectious disease-induced self-reactivity. Here, we have identified an immunodominant epitope derived from the S. typhimurium GroEL molecule. This epitope is presented by the mouse H2-T23-encoded class Ib molecule Qa-1 and was recognized by CD8+ cytotoxic T lymphocytes induced after natural infection. S. typhimurium-stimulated cytotoxic T lymphocytes recognizing the GroEL epitope cross-reacted with a peptide derived from mouse heat shock protein 60 and recognized stressed macrophages. Our results indicate involvement of MHC class Ib molecules in infection-induced autoimmune recognition and indicate a mechanism for the etiological link between Gram-negative bacterial infection and autoimmunity.
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PMID:Molecular mimicry mediated by MHC class Ib molecules after infection with gram-negative pathogens. 1065 13

Various lines of evidence suggest a close relationship between heat shock proteins (hsp) and several autoimmune diseases such as arthritis, diabetes and multiple sclerosis. While enhanced expression of hsp in autoimmune diseases is often regarded as a non-specific bystander effect of the inflammatory process, surprisingly little is known on hsp regulation by inflammatory mediators such as cytokines. In this study cytokine-induced expression of hsp60, hsp27 and alphaB-crystallin was studied in cultures of primary human adult astrocytes at the mRNA as well as at the protein level. We show differential hsp expression patterns in response to pro-inflammatory and immunoregulatory cytokines. Hsp60 expression was found to be enhanced in response to cytokines as diverse as IL-1beta, TNF-alpha, IL-4, IL-6 and IL-10. Upregulation of hsp27, however, was primarily induced by immunoregulatory cytokines like IL-4, IL-6 and TGF-beta whereas alphaB-crystallin expression was found to be enhanced by the pro-inflammatory cytokine TNF-alpha only. None of the cytokines studied was able to enhance expression of all three hsp simultaneously. These results show that in human astrocytes induced expression of hsp27 and alphaB-crystallin is dependent on the presence of a defined set of stimuli, while induced expression of hsp60 is a much less selective event. This highly differential pattern of hsp expression in response to inflammatory mediators known to play an important role in the pathogenesis of autoimmune diseases indicates that hsp responses are specific rather than non-specific bystander responses.
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PMID:Differential expression of stress proteins in human adult astrocytes in response to cytokines. 1081 78

Abnormal forms of Chlamydia trachomatis have been induced in vitro by a variety of methods including nutrient deprivation, addition of cytokines and addition of antibiotics. These forms have been shown to have altered morphology and infectivity and have been implicated in persistent infections in vivo although there is little direct evidence for their presence. Likely sites for abnormal forms in vivo are the genital tract and the synovial tissue of reactive arthritis patients, and T cells isolated from the synovial tissue have been shown to be specific for chlamydial antigens, in particular the Hsp60. Since T cell specificity is so important in reactive arthritis disease the antigenic composition of abnormal forms induced by Interferon-gamma and amino acid deprivation has been examined by western blotting in two strains of C. trachomatis belonging to different biovars. The degree of abnormality of the organisms was found to increase as the treatments became more severe. No simple patterns of antigenic changes were found and differences in the antigenic composition were seen in abnormal forms induced by the different treatments and also in the different strains.
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PMID:Induction of abnormal Chlamydia trachomatis by exposure to interferon-gamma or amino acid deprivation and comparative antigenic analysis. 1137 24

Adjuvant arthritis (AA) is an experimental model of autoimmune arthritis that can be induced in susceptible strains of rats such as inbred Lewis upon immunization with CFA. AA cannot be induced in resistant strains like Brown-Norway or in Lewis rats after recovery from arthritis. We have previously shown that resistance to AA is due to the presence of natural as well as acquired anti-heat shock protein (HSP) Abs. In this work we have studied the fine specificity of the protective anti-HSP Abs by analysis of their interaction with a panel of overlapping peptides covering the whole HSP molecule. We found that arthritis-susceptible rats lack Abs to a small number of defined epitopes of the mycobacterial HSP65. These Abs are found naturally in resistant strains and are acquired by Lewis rats after recovery from the disease. Active vaccination of Lewis rats with the protective epitopes as well as passive vaccination with these Abs induced suppression of arthritis. Incubation of murine and human mononuclear cells with the protective Abs induced secretion of IL-10. Analysis of the primary and tertiary structure of the whole Mycobacterium tuberculosis HSP65 molecule indicated that the protective epitopes are B cell epitopes with nonconserved amino acid sequences found on the outer surface of the molecule. We conclude that HSP, the Ag that contains the pathogenic T cell epitopes in AA, also contains protective B cell epitopes exposed on its surface, and that natural and acquired resistance to AA is associated with the ability to respond to these epitopes.
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PMID:Resistance to adjuvant arthritis is due to protective antibodies against heat shock protein surface epitopes and the induction of IL-10 secretion. 1205 66

Chaperonins are oligomeric proteins that assist in the folding of nascent or denatured proteins. Bacterial chaperonins are strongly immunogenic and can cause tissue pathology. They have been implicated in infection, autoimmune disease, and idiopathic or multifactorial diseases, such as arthritis and atherosclerosis. Chaperonin 60 proteins are also involved in prion diseases. In the past few years, much progress has been made in unravelling the involvement of various bacterial and mammalian chaperonin 60 (Cpn 60 or hsp 60) proteins in such diseases, and in proposing mechanisms for their biological actions, although we are still some way from a full understanding of chaperonin action that might lead to immunotherapeutic approaches. This review focuses on the current knowledge of the roles of Cpn 60 in the pathology of infectious and immune diseases, and discusses models for the actions of this molecule. Some potential therapeutic strategies will also be reviewed.
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PMID:Chaperonins in disease: mechanisms, models, and treatments. 1214 8

Adjuvant arthritis (AA) is an autoimmune disease inducible in rats involving T cell reactivity to the mycobacterial 65-kDa heat shock protein (HSP65). HSP65-specific T cells cross-reactive with the mammalian 60-kDa heat shock protein (HSP60) are thought to participate in the modulation of AA. In this work we studied the effects on AA of DNA vaccination using constructs coding for HSP65 (pHSP65) or human HSP60 (pHSP60). We found that both constructs could inhibit AA, but that pHSP60 was more effective than pHSP65. The immune effects associated with specific DNA-induced suppression of AA were complex and included enhanced T cell proliferation to a variety of disease-associated Ags. Effective vaccination with HSP60 or HSP65 DNA led paradoxically to up-regulation of IFN-gamma secretion to HSP60 and, concomitantly, to down-regulation of IFN-gamma secretion to the P180-188 epitope of HSP65. There were also variable changes in the profiles of IL-10 secretion to different Ags. However, vaccination with pHSP60 or pHSP65 enhanced the production of TGFbeta1 to both HSP60 and HSP65 epitopes. Our results support a regulatory role for HSP60 autoreactivity in AA and demonstrate that this control mechanism can be activated by DNA vaccination with both HSP60 or HSP65.
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PMID:Inhibition of adjuvant arthritis by a DNA vaccine encoding human heat shock protein 60. 1221 65


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