UMLS:C0003864 - FACTA Search

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Query: UMLS:C0003864 (arthritis)
69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Collagen arthritis is induced in inbred rats with the injection of native type II collagen. The pathogenesis of this experimental autoimmune disease is T cell dependent. This study demonstrates that collagen-specific T cells, derived from pathogenic and nonpathogenic rat T cell lines, both recognize the same peptide epitope. The epitope, consisting of amino acids 58-73 of cyanogen bromide fragment 11 of type II collagen, was as effective as whole collagen in stimulating a panel of collagen-specific rat/mouse T cell hybridomas. This peptide may, therefore, constitute a dominant epitope for CD4+ rat T cells in their response to type II collagen. Administration of the peptide to either neonatal or adult rats prevented the subsequent induction of experimental arthritis with whole collagen, demonstrating that the in vivo response to this dominant epitope is, therefore, relevant in the pathogenesis of arthritis. Despite its ability to prevent collagen-induced arthritis, administration of this peptide in incomplete Freund's adjuvant intradermally did not induce disease.
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PMID:Prevention of experimental autoimmune arthritis with a peptide fragment of type II collagen. 768 Jun 9

Collagen-induced arthritis (CIA) can be transferred from DBA/1 to SCID mice when native type II collagen (CII) is administered together with spleen cells, arthritis appearing some 14 days after cell transfer. In the present study, we demonstrate that both donor T- and B-lymphocyte populations play a role in this model, and that arthritis arises in SCID recipients of either murine or bovine native CII. Furthermore, the requirement for administration of soluble native CII can be replaced by subarthritogenic doses of serum from Wistar rats with CIA. In this case a fully developed arthritis appears as early as 2 days after cell transfer. However, protein G-purified IgG from CIA rat serum together with splenocytes from arthritic DBA/1 mice does not transfer arthritis. A key role of B cells in this model appears to be the production of a humoral arthritogenic factor since arthritis can be successfully transferred to SCID mice by CIA rat serum administered together with a B cell-depleted splenocyte population consisting of T cells and donor-histocompatible antigen-presenting cells. By contrast, transfer of disease cannot be achieved by co-administration of CIA rat serum and purified donor T cells, indicating that the presence of donor antigen-presenting cells is a requirement for adoptive transfer of arthritis. We propose that joint damage initiated by arthritogenic product(s) of the B cell lineage releases soluble antigens that are presented to T cells which perpetuate the disease. The finding that arthritis can be generated in SCID recipients of CIA rat serum together with splenocytes from non-arthritic DBA/1 mice immunized with denatured CII supports the hypothesis that T cells with specificity for denatured joint components perpetuate disease initiated by humoral factors.
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PMID:The role of the B cells in the adoptive transfer of collagen-induced arthritis from DBA/1 (H-2q) to SCID (H-2d) mice. 770 6

The induction of arthritis in DBA/1 mice usually requires immunization with the antigen type II collagen emulsified with Mycobacterium tuberculosis in oil. Here we describe that interleukin 12 (IL-12) can replace mycobacteria and cause severe arthritis of DBA/1 mice when administered in combination with type II collagen. Immunization of DBA/1 mice with type II collagen emulsified in oil alone resulted in a weak immune response, and only a few animals (10-30%) developed arthritis. Administration of IL-12 for 5 days simultaneously with each immunization strongly enhanced the anti-type II collagen immune response. Collagen-specific interferon gamma (IFN-gamma) synthesis by ex vivo activated spleen cells was enhanced 3- to 10-fold. IFN-gamma was almost completely produced by CD4+ T cells. Furthermore, the production of collagen-specific IgG2a and IgG2b antibodies was upregulated 10- to 100-fold. As a consequence, the incidence of arthritis in the group of mice immunized with collagen plus IL-12 was very high (80-100%). The developing arthritis was severe, involving approximately 50% of all limbs with strongly increased footpad thickness in most cases. Furthermore, histological examination revealed massive, mainly polymorphonuclear cell infiltration, synovial hyperplasia, cartilage and bone destruction, as well as new bone formation. In many cases, this resulted in the complete loss of joint structure. Neutralization of IFN-gamma in vivo prevented the development of arthritis in collagen-immunized and IL-12-treated mice. In conclusion, our data show that in vivo administered IL-12 can profoundly upregulate a T helper I-type autoimmune response, resulting in severe joint disease in DBA/1 mice.
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PMID:Administration of interleukin 12 in combination with type II collagen induces severe arthritis in DBA/1 mice. 776 7

Collagen-induced arthritis (CIA) is an animal model of auto immune polyarthritis, sharing similarities with rheumatoid arthritis (RA). Paradoxally, susceptibility to mouse CIA is controlled by the H2A loci (DQ homologous) while RA is linked to HLA.DR genes (H2E homologous). We recently showed that the E beta d molecule prevents CIA development in susceptible H2q mice. We addressed the question of whether H2Eb polymorphism will influence CIA incidence as HLA.DRB1 polymorphism does in RA. In F1 mice, only H2Ebd and H2Ebs molecules showed protection. Using recombinant B10.RDD (Ebd/b) mice, we found that CIA protection was mediated by the first domain of the E beta d molecule. Using peptides covering the third hypervariable region of the E beta chain, we found a perfect correlation between presentation of E beta peptides by the H2Aq molecule and protection on CIA. Therefore, the mechanism by which H2Eb protects against CIA seems to rely on the affinity of E beta peptides for the H2Aq molecule.
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PMID:Polymorphism of the MHC class II Eb gene determines the protection against collagen-induced arthritis. 779 66

The objective of this study was to analyse the anti-inflammatory and immunosuppressive properties of 6-hydroxydopamine (6-OHDA), a well known sympatholytic compound. Collagen type II arthritis, a T cell-dependent autoimmune disease, was significantly suppressed by a short-term administration of 6-OHDA at the time of the disease onset. Similar outcome was observed when in vivo models of T cell-dependent and independent inflammatory reactions were applied. In contrast, long-term pretreatment with 6-OHDA and hence efficient sympatholysis did neither affect the course of arthritis nor the outcome of T cell-dependent and independent inflammatory reactions. These findings, together with evidence of dose-dependent in vitro inhibitory effects of 6-OHDA on lymphocyte proliferation and differentiation, indicate that the anti-inflammatory features of this compound are mediated through a direct action on effector cells rather than by sympatholysis.
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PMID:Immunomodulating and anti-inflammatory properties of the sympatholytic compound 6-hydroxydopamine. 782 66

Collagen-Induced Arthritis (CIA) is an experimentally induced and genetically controlled animal model of chronic joint inflammation. In rats, there are informative strain differences in susceptibility to CIA. DA rats (RT1avl) develop severe CIA after immunization with bovine (BII), chick (CII), or homologous rat (RII) type II collagens. In contrast, the MHC-congenic DA. 1N(BN) and WF.1N(BN) rats (RT1n) are relatively resistant to CIA and develop moderate CIA in response to immunization with CII but not BII or RII. We previously found that simultaneous infection with rat cytomegalovirus (RCMV) greatly exacerbates the severity of arthritis that develops in BII-immunized DA rats. To examine the mechanism of RCMV amplification of CIA, the effect of simultaneous infection with RCMV on arthritis and autoimmunity to type II collagen was determined in WF.1N and DA.1N rats after immunization with BII, CII and RII. RCMV increased the incidence of CIA and the level of autoimmunity to type II collagen (skin-testing and IgG antibody titer) selectively in DA.1N and WF.1N rats immunized with CII, but not in littermates immunized with BII, although the transient reversal of CD4+/CD8+ mononuclear cell ratios in peripheral blood that is associated with RCMV infection occurred equally in both BII- and CII- immunized DA.1N rats. Likewise, RCMV infection moderately increased the levels of anti-RII autoimmunity and arthritis in DA rats sub-optimally immunized with RII but had no consistent effect on either anti-RII immunity or arthritis in RII-immunized DA.1N and WF.1n rats. The data show that RCMV augments arthritis only in rats that are genetically susceptible to CIA and that are appropriately immunized with a species of type II collagen that is arthritogenic for the MHC-haplotype being tested. Two possible mechanisms are suggested by these data: RCMV-associated increases in anti-RII autoimmunity in rats with CIA may result from amino acid sequence homologies between RCMV and type II collagen; alternatively, virus-induced pro-inflammatory cytokines may activate RII-reactive lymphocytes thereby potentiating autoimmunity and arthritis.
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PMID:Exacerbation of collagen-induced arthritis in rats by rat cytomegalovirus is antigen-specific. 785 3

Changes in the spinal expression of the opioid precursor and prodynorphin, which has been implicated in the response to peripheral inflammation, were examined with semi-quantitative in situ hybridization histochemistry in rats subjected to collagen II-induced arthritis. The effects of glucocorticosteroid treatment on the basal and inflammation-induced prodynorphin expression were evaluated. Collagen II-induced arthritis caused a 16-fold increase in prodynorphin mRNA levels which comprised all neurons expressing low levels under normal conditions. In the superficial dorsal horn, one group of neurons of a large size reacted with a dramatic increase of prodynorphin mRNA, while another group of small neurons exhibited a moderate elevation of prodynorphin mRNA levels. In the deep dorsal horn of arthritic rats, most prodynorphin neurons were large and showed high prodynorphin mRNA levels. Systemic treatment with the glucocorticosteroid budesonide attenuated the arthritis-induced increase of prodynorphin mRNA expression in a topospecific manner. The budesonide-induced reduction of prodynorphin mRNA levels was more pronounced in the deep dorsal horn than in the superficial dorsal horn. Budesonide treatment of control animals caused a small, but significant increase in prodynorphin mRNA levels in the superficial laminae I/II without affecting prodynorphin mRNA levels in the deep dorsal horn. The degree of arthritis correlated closely with spinal prodynorphin mRNA levels. The tight correlation between severity of arthritis and prodynorphin mRNA levels in non-treated and corticosteroid-treated arthritic rats suggests that spinal prodynorphin expression is a good parameter for the evaluation of the influence of peripheral inflammation and of the efficacy of analgesic/anti-inflammatory drugs in its treatment. Opposite effects of budesonide on basal and inflammation-induced prodynorphin expression may involve a spinal site of action in addition to peripheral anti-inflammatory mechanisms. We suggest that the collagen II-induced arthritis in the rat is an excellent model for human rheumatoid arthritis allowing for the study of molecular plasticity of anti-inflammatory and anti-nociceptive drug action at different levels of the neuroaxis.
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PMID:Spinal prodynorphin gene expression in collagen-induced arthritis: influence of the glucocorticosteroid budesonide. 789 56

Collagen-induced arthritis (CIA) is an animal model for the human autoimmune disease rheumatoid arthritis (RA). CIA can be induced in several species including primates by immunization with heterologous type-II collagen (CII). Polyclonal antibodies are formed upon immunization with CII that exhibit a broad range of epitope specificities (some that cross-react with hose CII); however, only antibodies directed against certain specific epitopes on CII are arthritogenic. Recently, the importance of cognate interactions between T-cells and B-cells to the induction of CIA was demonstrated by administration of monoclonal antibodies against a T-cell surface protein, gp39. Blocking the interaction of T-cell gp39, with its receptor/ligand on the surface of B-cells (CD40), completely blocked induction of CIA in mice. A concomitant reduction in the level of anti-CII IgG produced in anti-gp39-treated animals was observed, demonstrating the crucial importance of T-cell:B-cell interactions via gp39:CD-40 binding to the primary immune response to CII in vivo and therefore to the induction of CIA. Other features of CIA are important in elucidating the condition and this article will deal with some important issues.
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PMID:Collagen-induced arthritis as a model of rheumatoid arthritis. 792 7

Collagen-induced arthritis (CIA) is an animal model of autoimmune inflammatory polyarthritis that has features similar to rheumatoid arthritis (RA). Much like RA, susceptibility to mouse CIA is influenced by the major histocompatibility complex (MHC), H-2, and restricted to the H-2q and H-2r haplotypes. Whereas the role of the H-2A molecule in susceptibility to CIA is well established, little is known about the role of H-2E molecule in the disease. In this study, we analyzed the effect of a transgenic E beta d molecule on CIA susceptibility in a recombinant mouse B10.RQB3, which expresses the CIA susceptible Aq genes and an Eak gene, but does not produce an E molecule since Ebq is nonfunctional. In the presence of an Ebd transgene, a viable E molecule is generated. Whereas B10.RQB3 were susceptible to CIA, B10.RQB3-E beta d+ showed a dramatic reduction in the incidence of arthritis as well as a decrease in the level of anti-mouse and anti-bovine CII antibodies in their serum. No clear cut differences in the expression of T cell receptor (TCR) V beta was observed between E beta d+ and E beta d- transgenic mice. Mechanisms underlying the protective effect of E beta d transgenic molecule on CIA may shed light on how HLA-DR molecules influence human RA.
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PMID:Protective role of major histocompatibility complex class II Ebd transgene on collagen-induced arthritis. 793 Oct 88

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