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)

This experimental study was undertaken to clarify whether beta 2-microglobulin (B2M) deposits are the cause or merely the consequence of arthritis or osseous changes in chronic renal failure. Twenty-one heminephrectomized, male inbred DBA/1J mice were divided into 3 groups of 6 animals and a group of 3 mice. Collagen arthritis was produced by the intradermal injection of an emulsion of bovine collagen type II and complete Freund's adjuvant in groups 1, 2 and 4. Human urine derived B2M, 100 micrograms and 300 micrograms was then given subcutaneously to group 1 for up to 10 days and also to the 6 mice in group 3 without arthritis. Three mice in group 4 received horse myoglobin 100 micrograms daily for 1, 3 and 5 days as a control. Regardless of the presence of arthritis or osseous changes, B2M was deposited predominantly in the bone marrow and synovium of the B2M treated mice in groups 1 and 3. On the other hand, group 2 which had not been given B2M had no deposits. Deposits of myoglobin were not seen in group 4 mice. These findings suggest that B2M is deposited in the bone marrow and synovium as a primary event.
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PMID:Beta 2-microglobulin has a strong affinity to bone marrow and synovium: an experimental study. 860 54

Collagen-induced arthritis (CIA) is an experimental autoimmune disease induced by immunization with collagen type II (CII). We studied CIA in CD4- or CD8-deficient DBA/1 mice to further define the roles of CD4+ and CD8+ T cells in the disease. CD4-deficient mice developed severe arthritis, and no differences in incidence, clinical course, and severity were observed between CD4 -/- and CD4 +/- mice. Proliferative responses of lymph node T cells to CII was, however, reduced in CD4 -/- mice, and inflamed joints revealed relative accumulation of CD4-CD8-TCR(alpha)(beta)+ cells. A CII-specific T cell line generated from CD4-deficient mice responded to CII in a MHC-restricted fashion and had a CD4-CD8-TCR(alpha)(beta)+ phenotype. Disease incidence in CD8 -/- mice was significantly decreased compared with CD8 +/- mice, even though the severity of arthritis in arthritic mice was not different. These results suggests a role for CD8+ T cells in initiating CIA. Interestingly, CD8-deficient mice were more susceptible to a second induction of arthritis after remission of initial disease, pointing towards an immunoregulatory role for CD8+ T cells. CD8-deficient mice did not, however, show any defect in oral tolerance induction using CII. Taken together, our findings demonstrate that CD4-CD8-TCR(alpha)(beta) cells can trigger systemic arthritis in CD4-deficient mice and that CD8+ T cells can play dual and opposing roles, important both in initiation of CIA and in providing resistance to reinduction of CIA after recovery from initial disease.
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PMID:Collagen-induced arthritis in CD4- or CD8-deficient mice: CD8+ T cells play a role in initiation and regulate recovery phase of collagen-induced arthritis. 866 29

Collagen-induced arthritis (CIA) in susceptible strains of mice is an animal model of T cell-mediated inflammatory polyarthritis. Analysis of T cell receptor (TCR) V beta gene usage in cells isolated from arthritic joints of BUB/BnJ (BUB) mice (H-2q, TCR V beta a) showed that TCR V beta chain gene usage was limited to TCR V beta 3 and V beta 10 gene families. All of the BUB mice immunized with a mixture of TCR V beta 3 and TCR V beta 10 peptides, but not with control TCR V beta 14 peptide, were refractory to the induction of CIA. Immunization with TCR V beta 3 and V beta 10 peptides completely blocked the development of clinical and subclinical inflammation, formation of pannus and synovial hyperplasia, and the erosion of cartilage and bone. Further studies revealed that preimmunization of BUB mice with V beta 10 peptide alone was sufficient to render the mice resistant to CIA. Analysis of TCR V beta chain gene expression in lymph node cells from arthritic and arthritis-protected mice showed the expression of TCR V beta 10 subfamily in all of the arthritic mice, but not in arthritis-protected mice. Immunization with TCR V beta peptides did not diminish the humoral responses to chicken type-II collagen and also elicited significant levels of anti-V beta 3 and anti-V beta 10 peptide antibodies. Antibodies cross-reactive with mouse chicken type-II collagen were detected in both the arthritic and arthritis-protected mice. Adoptive transfer of serum from arthritis-protected BUB mice significantly delayed the onset (P < 0.005) of arthritis in recipient BUB mice. In contrast, mice injected with serum from arthritic mice had early onset of arthritis. These results demonstrate that immunization of BUB mice with TCR V beta chain peptides elicited antibodies reactive with the self-TCR and prevented the induction of collagen-induced arthritis by eliminating or downregulating pathogenic T cells and consequently blocking the development of humoral immune response. These findings may have clinical applications in treating human autoimmune diseases characterized by common TCR gene usage.
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PMID:Immunization with T cell receptor V beta chain peptides deletes pathogenic T cells and prevents the induction of collagen-induced arthritis in mice. 867 97

Collagen-induced arthritis in susceptible mice is widely accepted as an experimental model for human rheumatoid arthritis (RA). We have investigated the role of the Mac-1 integrin beta 2 in the development and maintenance of arthritis by means of in vivo administration of 5C6 monoclonal antibody (mAb) to block this receptor. Injection of a single dose of 5C6 mAb (0.5 mg, intraperitoneally) prior to the expected onset of collagen-induced arthritis in DBA/1 mice diminished the severity of subsequent disease in these animals, as assessed both clinically and histologically (P < 0.01, chi 2). In the DBA/1 to severe combined immunodeficiency (SCID) transfer model of arthritis, the incidence of clinical arthritis was significantly reduced in SCID mice receiving maintained 5C6 treatment commencing the day prior to administration of donor splenocytes. Histological evaluation of joints from animals without clinically evident arthritis confirmed the absence of an inflammatory infiltrate in 22/27 joints examined. In a minority of these joints, however, synovial hyperplasia was apparent. In contrast, delaying antibody administration until 10 days after donor spleen cell transfer failed to protect three of five SCID recipients. These results confirm a functional role for Mac-1 in the generation of collagen-induced arthritis in mice. Since mAb 5C6 is non-cytotoxic, its action must be by blockade of the interactions between Mac-1 and its natural ligand(s). Our findings support the hypothesis that cells expressing Mac-1 play an important role in the induction and maintenance of joint damage in collagen-induced arthritis.
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PMID:Transfer of type II collagen-induced arthritis from DBA/1 to severe combined immunodeficiency mice can be prevented by blockade of Mac-1. 869 Apr 67

Collagen-induced arthritis can be transferred into severe combined immunodeficiency (SCID) mice by spleen cells from diseased DBA/1 mice. The development of arthritis in SCID animals can be prevented by infection ex vivo of DBA/1 spleen cells with retroviruses expressing the monomeric soluble human p75 tumor necrosis factor (TNF) receptor (TNF-R). In addition, a vector engineered to express a polycystronic mRNA with TNF-R and the herpes simplex virus thymidine kinase (HSVtk) gene, while producing low levels of TNF-R, had a limited effect which could be blocked by treating the animals with ganciclovir. A retroviral vector expressing the HSVtk gene alone had no effect on this arthritis transfer model with or without ganciclovir. Serum levels of TNF-R did not correlate with clinical signs, however, lower anti-collagen antibody levels corresponded with lack of clinical symptoms. These results indicate that local production of cytokine inhibitor is essential for therapeutic purposes while systemic levels may not be required.
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PMID:Inhibition of transfer of collagen-induced arthritis into SCID mice by ex vivo infection of spleen cells with retroviruses expressing soluble tumor necrosis factor receptor. 875 12

Collagen-induced arthritis (CIA) is an animal model of auto-immune inflammatory polyarthritis which has features similar to rheumatoid arthritis (RA). Much like RA, susceptibility to mouse CIA is influenced by the major histocompatibility complex (MHC) and is restricted to the H2 haplotypes q and r. In previous experiments, we have found that the introduction of an H2-Ebd transgene in H2-Aq CIA-susceptible mice was able to protect these mice against disease development. More recently, we have proposed that the polymorphism of the first domain of the Ebeta molecule modulates this protection, and that the presentation of a peptide from the third hypervariable region of the Ebeta chain by the H2-Aq molecule plays an important role in this mechanism. In the present report, we investigated whether the H2-E-mediated protection is H2-Aq-specific and whether the source of collagen has any influence. While the source of collagen had no effect on the protection, our results showed that the H2-E molecule failed to protect B10.RIII (H2(r)) mice against CIA. Further, the H2 haplotype r exerted a negative effect on the Ebetad-mediated protection in H2-Aq-restricted disease. Our results provide additional proof that self-MHC-derived peptides, such as Ebeta peptides, may play an important role in the T-cell repertoire education and/or modulation of the T-cell response in the periphery.
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PMID:H2-A polymorphism contributes to H2-Ebeta-mediated protection in collagen-induced arthritis. 878 Nov 24

Collagen-induced arthritis is an autoimmune model disease induced in the DBA/1 mouse immunized with type II collagen (CII). Both T and B cells play a critical role for the induction of arthritis. Draining lymph nodes from CII-immunized mice contain high numbers of CII-specific B cells, which are isotype switched and V gene selected. In the present study we analyze the V region gene usage and epitope specificity of CII-reactive B cell hybridomas, randomly isolated from the primary and the secondary response in mice immunized with rat CII we make the following conclusions. 1) There are major epitopes in the native CII molecule to which the B cells preferentially respond. 2) B cells specific for the same epitope show a preferential pairing of certain VH/VK genes or a biased usage of individual VH (VHJ558 and VHX24) or VK genes (VK21). 3) The V genes are germ line encoded in the primary response and somatically mutated in the secondary response. Somatic mutations give the Abs cross-reactivity between CII epitopes, and epitope shift, i.e., another epitope within the CII molecule is recognized. 4) There is a sharing of certain V genes in B cell clones specific for different epitopes, indicating structural similarities of the different CII epitopes.
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PMID:The B cell response to autologous type II collagen: biased V gene repertoire with V gene sharing and epitope shift. 880 43

Collagen-induced arthritis (CIA), an autoimmune arthritis model, is elicited by the immunization of genetically susceptible strains of mice with type II collagen (CII). We have analyzed the molecular interactions that occur during the presentation of the immunodominant determinant within CII(257-270) by the murine class II susceptibility allele, I.Aq. Utilizing a soluble I-A binding assay and clonally distinct CII-specific T cells, we have identified the residues that control the ability of the CII(257-270) peptide to bind to I-Aq and those that interact with the TCR. In competitive binding assays with a panel of analog peptides, only two residues within CII(257-270) were found to participate in the binding of this peptide to I-Aq, residues 260 (Ile) and 263 (Phe). When these substitutions were combined into a single peptide, no binding of the peptide to I-Aq could be detected. Although no other substitutions decreased the binding affinity of the peptides, substitution of several amino acid residues lying outside of the determinant core increased the peptide's affinity for I-Aq and in some instances greatly enhanced the potency of the peptide in stimulating T cells. In antigen presentation assays, clonotypic variation in the recognition of several analog peptides indicated that residues 261, 262, 264, 266, and 267 are likely TCR contact sites. Since residue 266 interacts with the TCR and is the only residue in this determinant that differs between chick/bovine CII and mouse CII, these data indicate that immunity to the autoantigen may play a role in this model.
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PMID:Identification of MHC class II and TCR binding residues in the type II collagen immunodominant determinant mediating collagen-induced arthritis. 880 2

Collagen type II-induced arthritis (CIA) is an experimental model of arthritis that has been successfully used to dissect the pathogenesis of human rheumatoid arthritis and to identify potential therapeutic targets. We have used this model to evaluate the role of T cell co-stimulation in both disease development and progression. T cell co-stimulation is provided by ligation of CD28 with either B7-1 or B7-2 present on antigen-presenting cells and can be prevented by a soluble form of CTLA-4 (CTLA-4Ig) which binds with high affinity to both B7-1 and B7-2. We found that administration of CTLA-4Ig at the time of immunization prevented the development of CIA and was associated with lack of lymphocyte expansion within the draining lymph node and failure to produce anti-collagen IgG1 or IgG2a antibodies. To determine which CD28 ligand plays a more dominant role in CIA, we treated mice with monoclonal antibodies (mAb) against either B7-1 or B7-2. Neither anti-B7-1 nor anti-B7-2 had any effect on the course of CIA when given alone, but resulted in reduced incidence and clinical scores when given together. Interestingly, when treatment was delayed until after the onset of clinical disease, both CTLA-4Ig or anti-B7-1 plus anti-B7-2 mAb still ameliorated disease. Effective treatment was associated with a reduction in interferon-gamma production by lymph node cells following stimulation in vitro, suggesting that Th1 responses were diminished. This study points to a critical role of CD28 co-stimulation in the development and perpetuation of CIA in DBA/1 mice. Interestingly, it demonstrates an active role for T cells in the later stages of this disease and implicates both B7-1 and B7-2-mediated co-stimulation in the pathogenesis of CIA.
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PMID:Prevention and amelioration of collagen-induced arthritis by blockade of the CD28 co-stimulatory pathway: requirement for both B7-1 and B7-2. 889 40

Collagen-induced arthritis (CIA) is an experimental autoimmune disease elicited in genetically susceptible strains of mice by immunization with heterologous type II collagen. This experimental disease is mediated by the immune response of both T cells and B cells, and susceptibility is restricted by the class II molecules of the MHC. In this study we identify specific epitopes bound by autoantibodies elicited through immunization of several haplotypes of C57BL/10 mice with chick alpha1 (II)-CB11. ELISA analysis using a panel of 15-mer murine type II collagen peptides revealed a pattern of autoantibody epitope specificity that was remarkably similar among CIA-susceptible and nonsusceptible congenic strains, regardless of class II haplotype. However, one epitope was identified that was bound only by autoantibodies from CIA-susceptible strains bearing I-A(q) (B10.Q and B10.QbetaBR). In addition, this epitope was also present within affinity-purified Ab obtained from the CIA-susceptible strain DBA/1 (I-A(q)). Analyses of immune serum from B10.Q and B10.QbetaBR mice revealed that a subset of the antibodies binding this epitope were of the IgG2 subclass, and therefore efficient at fixing complement, a requirement for pathogenicity of the Abs in CIA.
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PMID:Autoantibodies to murine type II collagen in collagen-induced arthritis: a comparison of susceptible and nonsusceptible strains. 894 30


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