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)

The mycobacterial 65 kDa heat shock protein (HSP65) is of critical significance in the model of adjuvant arthritis (AA). Arthritogenic and protective T cell clones obtained from arthritic rats recognized the 180-188 sequence of HSP65. Previous reports have shown that administration of HSP65 prior to disease induction led to resistance to arthritis in the AA model and in several other models of experimental arthritis. Here, we report the development of immunity to HSP65 and the critical 180-188 epitope during the course of AA. Following Mycobacterium tuberculosis (MT) immunization both antibodies and T cell responses to HSP65 were detected. Proliferative responses to the 180-188 epitope were seen exclusively in the local draining lymph node cells at day 14 after immunization. The anatomical distribution and course of T cell responses to HSP65 and its 180-188 epitope are compatible with T cell regulated control of the disease. Although lower HSP65 antibody levels were observed in the animals with severe arthritis, in individual animals no evidence was obtained for a relationship between development of HSP65 humoral immunity and arthritis severity. Nevertheless, during disease exacerbation, elicited by HSP65 immunization during disease development, elevated T cell responses against HSP65 and its 180-188 epitope were found. In contrast, we obtained evidence that successful transfer of arthritis resistance to naive recipients depends on the transfer of HSP65 specific T cells. On the basis of these results, it seems that HSP65 plays a crucial role in the T cell regulatory events involved in both the induction of, and protection against, AA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adjuvant arthritis and immunity to the mycobacterial 65 kDa heat shock protein. 149 83

Live recombinant vaccinia viruses, expressing antigens from pathogenic microorganisms, are studied for their use as vaccines designed for the protection against infectious diseases. Infections with these vaccinia virus recombinants, expressing proteins or epitopes from viruses, parasites, or bacteria, have resulted in the development of specific neutralizing antibodies or cytotoxic T lymphocytes. Here, we describe the generation of a recombinant vaccinia virus expressing the mycobacterial 65-kDa heat shock protein (HSP65). A vaccinia recombinant virus was constructed by placing the gene for the Mycobacterium bovis BCG HSP65 under control of a vaccinia virus promoter and inserting this mycobacterial gene in the thymidine kinase locus of the vaccinia virus genome. Mycobacterial HSP65 is a critical antigen in the autoimmune model of adjuvant arthritis induced in Lewis rats by the immunization with Mycobacterium tuberculosis. We report the induction of immunity directed to this mycobacterial HSP65 by testing for the presence of specific antibodies and T-cell proliferation. Furthermore, induction of such immunity resulted in a reduction of arthritis severity when given to rats before or, even more interestingly, during development of arthritis. Disease reduction was not found after administration of HSP65 in the absence of vaccinia virus as a vector when given during arthritis development. Therefore, recombinant vaccinia virus may offer new prospectives for specific intervention in autoimmunity.
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PMID:Modulation of experimental autoimmunity: treatment of adjuvant arthritis by immunization with a recombinant vaccinia virus. 190 72

Recognition of self protein epitopes, apart from those engaged in idiotypic network interactions and MHC restriction, is probably a physiological event in the normal functioning immune system. Furthermore T and B cells recognizing self antigens can be easily cloned from healthy individuals and sometimes be shown to confer autoimmune disease by passive transfer in the experimental situation. The issue is how potentially autoaggressive cells can become activated and how such activity can be contained safely. Experimentally, autoimmune disease can be evoked by immunization with autoantigens (encephalomyelitis, thyroiditis etc.) or with foreign antigens that feature antigenic relationships with self antigens (adjuvant arthritis). In both situations transfer of disease has been shown with cloned T cells of a single specificity. In addition, specific control of disease using the same cloned T cells has been achieved. Adjuvant arthritis has been illustrative in these respects. By means of specificity analysis of cloned T cells, a 65 kD heat shock protein of mycobacteria was identified as crucial in the disease. Immunization with this antigen has been found to prevent the development of disease, including forms elicited without mycobacterial involvement. Furthermore, vigorous immunological responses to HSP65 were found both in experimental animals and also in humans as a consequence of exposition to various infectious organisms. By their conserved nature HSPs have ample potential for dangerous mimicry. Recent evidence accumulated suggesting that the same HPS65 may be crucial in human chronic arthritis as well. Therefore it is hoped that extrapolation of the experimental findings to the human situation will help the development of specific means, either T cells or antigens, to control spontaneous autoimmune arthritis in man.
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PMID:Heat-shock proteins in autoimmune arthritis: a critical contribution based on the adjuvant arthritis model. 219 35

Chlamydia trachomatis infection of humans is commonly a localized inflammation that can result in infertility, blindness, and perhaps arthritis. The pathogenic process(es) that cause these sequelae are thought to be immunological. A 57-kD protein that is common among Chlamydia elicits ocular inflammation when introduced onto the conjunctivae of guinea pigs or nonhuman primates previously sensitized by chlamydial infection. This protein is thought to mediate the immunopathology that follows chlamydial infection. To more thoroughly characterize this chlamydial component, we cloned its gene from a C. psittaci strain and identified a particular recombinant that produced the 57-kD polypeptide. The recombinant gene product was immunoreactive with a monospecific anti-57-kD serum, and elicited an ocular inflammation similar to that produced by the 57-kD antigen isolated from chlamydiae. Sequencing identified two ORFs that encode polypeptides of 11.2 and 58.1 kD and are co-transcribed. These two polypeptides show homology with Escherichia coli groE and Coxiella burnetii htp heat-shock proteins. Striking homology (greater than 50%) was found between the 57-kD protein and the HtpB, GroEL, 65-k Mycobacterium tuberculosis and Hsp60 proteins. Thus, the 57-kD chlamydial protein, previously implicated as mediating a deleterious immunologic response to chlamydial infections, is a stress-induced protein similar to those that occur universally in both prokaryotic and eukaryotic organisms.
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PMID:Chlamydial disease pathogenesis. The 57-kD chlamydial hypersensitivity antigen is a stress response protein. 257 68

Sheep infected with maedi visna virus were tested for immune reactivity to recombinant HSP65 and tuberculin PPD from mycobacteria. The results showed that both naturally and experimentally infected animals had elevated IgM but not IgG or IgA antibodies to HSP65 from Mycobacterium leprae or M. bovis. In experimentally infected animals, the elevated IgM antibodies appeared in blood from about 3 to 4 weeks postinfection. Increased T cell proliferative responses to HSP65 and PPD were also found in both naturally and experimentally infected sheep. The T cell responses to HSP65 were substantially inhibited by antibodies to ovine major histocompatibility complex class II molecules, indicating that the responses were class II restricted. Increased expression of a putative HSP65 molecule was observed in synovial membranes from sheep infected with maedi visna virus and goats infected with the related, caprine arthritis encephalitis virus. The results thus show that lentivirus infection induces T and B cell anti-HSP65 immune responses and suggest that synovial inflammation may be due, at least in part, to T and B cell recognition of HSP65-like molecules expressed in joints.
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PMID:T and B cell responses to mycobacterial 65-kDa heat-shock protein in sheep infected with maedi visna virus. 753 20

Oral desensitization or oral tolerance is induced by giving antigenic peptides by the mucosal route. In man only the oral route has been used up to now. Experiments in animal models of human autoimmune diseases, have shown that it is not necessary to use the primary antigen responsible for disease induction. Antigens implicated in secondary immune phenomenon can act similarly by means of the so-called "bystander suppression". Thus for diseases such as multiple sclerosis (MS) and rheumatoid arthritis (RA) candidate antigens for desensitization are available. Many patients with MS have immunity to myelin basic protein (MBP). A recent controlled trial giving MBP to patients with MS is discussed (Weiner et al., Science 259, p. 1321, 1993). No clear-cut effect was obtained. Collagen II is used to induce experimental arthritis in rats; signs of immunity against it can be found in patients with RA. Collagen-induced arthritis has been successfully modified in animals by feeding of collagen II. In man one open uncontrolled trial and one other placebo controlled blind trial have been reported, and these are discussed (Trentham et al., Science 261, 1727, 1993). These trials suggest that oral desensitization might be useful and devoid of side effects. Subreum is a peptic E. coli extract containing heat shock protein 60. Its efficacy as a disease-controlling agent in RA has been documented (Clin. Exp. Rheum. 11, p. 121, 1993). It is given orally. Data suggesting that Subreum acts by oral desensitization are discussed. Considering the low incidence of side effects observed with oral desensitization, this therapeutic approach should also be tested in other forms of arthritis and other inflammatory diseases.
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PMID:Oral desensitization in the treatment of human immune diseases. 754 38

Rheumatoid arthritis (RA) is an autoimmune disease and rheumatoid factor (RF), anti-IgG, has been implicated in the pathogenesis, but the exact etiology remains unclear. There are data to suggest and infectious trigger to the autoimmune process, and mycobacteria are considered a candidate. Immunization of various animals with mycobacterial heat shock protein 65 (mhsp65) protects against subsequent autoimmune arthritis in a number of experimental models. Elevated anti-mhsp65 titres have been demonstrated in RA patients, together with specific T cells isolated from inflamed synovium. Mycobacterial hsp65 has also been implicated in other autoimmune disease and in atherosclerosis. The anti-mhsp65 and RF (IgG, IgM and IgA isotypes) titres were assayed by ELISA in 123 pairs of normal twins (61 monozygotic and 62 dizygotic, age 14-79 years), to examine the population distribution and inter-relationship of these antibodies. In addition, we studied the effects of age, sex, genetics and environment on antibody titres. IgG-RF and IgM-RF were detectable in all subjects and IgA-RF in 41 subjects. None of the RF isotypes showed any significant dependence on age or sex. There was a statistically significant correlation between twins for the IgG-RF and IgM-RF, and a positive but not significant correlation for the IgA-RF. All three correlations were stronger for monozygotic than dizygotic twins, reaching statistical significance for IgM-RF (P < 0.001), and this indicates that there is a genetic influence on RF titres. Anti-mhsp65 titres were detectable in 90.5% of the study group with a range of 0.15-19.7 AU/ml. There were weak correlations between twins, stronger for dizygotic than monozygotic twins. This suggests that familial influences on anti-mhsp65 titres are very small, with no evidence of any genetic influence at all. There was no significant relationship of anti-mhsp65 titre with age, sex or RF titres.
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PMID:Antimycobacterial hsp65 and rheumatoid factor titres in a population of normal twins: evidence of genetic control of rheumatoid factor. 766 85

Previous work has indicated that autoimmunity to the mammalian 60-kD heat shock protein (hsp60) may be necessary for the development of pristane-induced arthritis (PIA), a murine model of rheumatoid arthritis. To characterize the expression of hsp60 in murine joints, immunoblots of joint extracts and frozen histological sections prepared from normal or arthritic mice were probed with the hsp60-specific MoAb 4B989. Hsp60 could be detected in the joints of mice with PIA by both techniques, and was seen to be localized within the inflamed pannus using immunhistochemistry. Immunoblotting revealed that lower concentrations of hsp60 are also present in normal mouse joints, and that the level of expression increases with age, in parallel with greater susceptibility to PIA. In other studies, it was demonstrated that the titres of serum IgG antibodies reactive with the related mycobacterial hsp65, and the in vitro responsiveness of splenic T cells to hsp65, are both elevated in older mice. It is considered that the results are consistent with the hypothesis that PIA develops following environmental priming with mycobacterial hsp65, and the targeting of cross-reactive T cells to self-hsp60 in the joints.
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PMID:Expression of mammalian 60-kD heat shock protein in the joints of mice with pristane-induced arthritis. 856 93

The morphology of autoimmune hepatitis is characterized by portal-periportal predilection of necroinflammatory lesions. In comparison to the viral type of hepatitis severe piece-meal-necroses, the collapse of periportal parenchyma, and to a higher degree acinar transformation of hepatocytes are more prominent. The autoimmune hepatitis may start with acute disease displaying unusual clinical und histopathologic features. The postinfantile giant cell hepatitis seems to constitute a variant of autoimmune hepatitis. Autoimmune hepatitis has been reproduced in animal models and it could be demonstrated in rabbits that humoral immunity plays a role in tissue damage. The importance of cellular mechanisms could be analyzed in syngenic mice showing that the CD4-positive lymphocytes play a pivotal role. The most promising candidate antigen seems to be the asialoglycoprotein-receptors including the liver specific protein (LSP). By immunohistologic analysis dense deposits of IgG could be demonstrated in sinusoids and on the membranes of hepatocytes. In accordance with in vitro data the determination of CD4 positive lymphocytes in the tissue was found to play a decisive role in cellular immune reaction. The HSP65 molecule seems to evoke mechanisms that have been shown to play a pathogenetic role in experimental arthritis.
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PMID:[Autoimmune hepatitis]. 860 Jun 83

Studies of the immune response of mammals to infectious agents have revealed that members of the hsp60 and hsp 70 family are highly immunodominant. Given their high conservation during evolution this was surprising, because of the apparent risk of triggering of autoimmunity and autoimmune disease during the defense of a mammal against infection. However, detailed studies of the immune responses to HSP in models of autoimmune diseases in animals resulted in a change of the view that autoimmunity necessarily leads to autoimmune disease. It has been found that modulation of autoimmunity to HSP is one way to prevent autoimmune disease. At least in some cases even treatment of autoimmune diseases by immunization with heat shock protein appears feasible. This was shown in adjuvant arthritis in Lewis rats and insulin dependent diabetes in NOD mice. Hsp60 and hsp70 are ubiquitous proteins. Their involvement in regulatory loops of autoimmunity may serve as basis for the development of strategies, to prevent and/or treat autoimmune diseases even without knowledge of the causative (auto-)antigen.
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PMID:Infection, autoimmunity and autoimmune disease. 885 85


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