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

Superoxide anion, a highly reactive free radical, was generated in vitro using enriched purified xanthine oxidase. Collagen solutions exposed to superoxide radical failed to gel normally when heated to 37 degrees C. The magnitude of the inhibition of gelation was propotional to duration of exposure and to flux of superoxide. Since inhibition of collagen gelation reflects alteration of collagen biochemistry, and/or collagen degradation, it is suggested that the action of free radicals produced in vivo by leukocytes may adversely affect the structural or functional integrity of cartilage and adjacent joint structures.
Arthritis Rheum 1979 Mar
PMID:Inhibition of collagen gelation by action of the superoxide radical. 21 93

Collagen induced arthritis is an experimental animal model of inflammatory polyarthropathy that has many features of human rheumatoid arthritis. Type II collagen is the major matrix protein of hyaline cartilage and is a sequestered protein which can be presented as an autoantigen under certain conditions. To induce CIA, type II collagen is injected intradermally with complete Freund's adjuvant. Susceptibility to CIA is dependent on the presence of the trimolecular complex: 1) the arthritogenic epitope on the type II collagen; 2) a class II MHC molecule on the accessory cell presenting the arthritogenic epitope; and 3) T cells expressing specific V beta chains in their TCRs. Complement and other non-MHC background genes also may play a role in susceptibility to CIA. Both cell mediated and humoral immunity are involved in the pathogenesis of CIA. To date immunotherapies that have modulated CIA include use of anti-class Ii antibodies, anti-lymphokines, and monoclonal antibodies directed against specific cellular markers. All of these therapies are able to modulate disease to some extent but lack the specificity and efficacy to make them practical for widespread use in human disease. Most promising, is the use of monoclonal antibodies directed against specific V beta TCR subsets. This is potentially a very specific and effective therapy because it will affect only the cells involved in disease while leaving the host otherwise immunocompetent. Therapies on the horizon include the use of synthetic peptides with sequences homologous to various regions on the TCR, immunotoxins, and superantigens to modulate the immune response and ameliorate disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunogenetics of collagen induced arthritis in mice: a model for human polyarthritis. 128 54

Collagen type II (CII) is a cartilage-specific matrix compound well known as an inducer of an experimental, T cell-dependent autoimmune arthritis, a disease which shows some similarities to human rheumatoid arthritis. Here we report on an HLA-DR7-restricted human CD4 T cell clone (TC9), which was isolated from a healthy donor and recognizes human CII. After screening CNBr fragments of CII and tryptic fragments derived thereof, the T cell epitope could be mapped to amino acid residues 271-285 of the triple helical region of CII that are located within CNBr fragment 11 [alpha 1 (II) CB11]. This epitope was confirmed by a synthetic peptide stimulatory for TC9. The T cell receptor beta chain of TC9 was cloned using the polymerase chain reaction; it comprises V beta 6.7 and contains besides J beta 2.3 and C beta 2 an as yet undescribed sequence for the D segment.
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PMID:Specificity and T cell receptor beta chain usage of a human collagen type II-reactive T cell clone derived from a healthy individual. 137 Apr 17

Type II native bovine collagen was used to induce arthritis in sheep. The sheep received a subcutaneous injection of collagen in Freund's adjuvant, and some sheep also received an intra-articular injection of collagen. The response to the collagen injections was monitored by measurement of antibody levels to bovine and ovine collagen in serum, synovial fluid and afferent lymph samples. There were antibodies in the normal sheep serum which reacted with native and denatured type II collagen, but there was a marked rise in serum and synovial fluid reactivity after subcutaneous injection of native collagen. In these sensitised sheep there was a further rise in antibody levels in the synovial fluid and afferent lymph samples after an intra-articular injection of collagen. There was little effect on antibody levels in the non-injected contralateral limb. Histological and immunohistochemical studies showed that the rise in antibody levels was associated with pathological changes to the synovium which were consistent with the development of arthritis. These changes were most severe in those joints of sensitized sheep which had received an intra-articular injection of collagen and were characterized by increased numbers of T cells in the synovial tissue, mainly of the CD4 phenotype. There was a marked increase in B cell expression by cells on the surface of the synovial intima, and accumulations of B and T cells were seen in the subsynovial tissues. Collagen-immune complex arthritis in sheep appears to be a useful large animal model of arthritis, with significant similarities to the arthropathies of other species, including man.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Type II collagen-immune complex arthritis in sheep: collagen antibodies in serum, synovial fluid and afferent lymph. 145 6

Collagen induced arthritis (CIA) is an animal model of inflammatory polyarthritis. Type II collagen is the major matrix protein of hyaline cartilage. Susceptibility to CIA is linked to the Major Histocompatibility Complex Class II genes but the presence of T cells expressing specific variable beta (V beta) chain of their T cell receptor (TCR) is also required. Pretreatment with the monoclonal antibody H57-597 directed against the TCR alpha beta framework prevented the onset of arthritis in the majority of animals. The depletion of the T cell population did not lead to any apparent health problems. These experiments demonstrate the important role of the alpha/beta T cell and its receptors in the CIA model. Further, anti-TCR alpha beta antibodies may be of value in the therapy of autoreactive disorders.
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PMID:Prevention of collagen induced arthritis in mice by treatment with an antibody directed against the T cell receptor alpha beta framework. 153 96

Collagen-induced arthritis (CIA) in rats, induced with homologous type II collagen (CII), is a genetically more restricted disease and has better resemblance to rheumatoid arthritis by its chronic disease course, than CIA induced with heterologous CII. The DA strain is highly susceptible to CIA induced with homologous CII, while the Lewis strain is resistant. (DAxLew)F1 is susceptible and backcrossing to Lewis reveals a close, but not complete, association of both arthritis and CII responsiveness to the RT1a haplotype. Analyses of congenic strains on DA and Lewis backgrounds suggest that expression of a major histocompatibility complex class II Ba molecule, encoded from the RT1Ba locus, is associated with arthritis susceptibility and CII responsiveness. The second exons coding for the first domains of the alpha and beta chains of both the RT1a and RT1l haplotypes were sequenced and the deduced amino acid sequences compared with the corresponding molecule associated with susceptibility to CIA in the mouse (H-2 Aq). The sequences of the respective alleles revealed no obvious structural homology explaining the extensive similarities in the development of chronic autoimmune arthritis. Instead, this finding implies that different trimolecular constituents (i.e. class II, T cell receptor, and CII peptides) may yield an antigen presentation event that is able to trigger a similar autoaggressiveness in the two rodent species.
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PMID:Homologous collagen-induced arthritis in rats and mice are associated with structurally different major histocompatibility complex DQ-like molecules. 153 78

Age-associated changes of the human synovium have been investigated by microarthroscopy, optical and electron microscopy, immunohistochemistry, and cytochemistry. The knee joints of nineteen 15- to 56-year-old subjects, classified as normal by inspection, were carefully examined by microarthroscopy; small synovial tissue biopsy specimens from both the suprapatellar pouch and the medial tibiofemoral gutter were taken. Microarthroscopy showed that the villi were more numerous and the vascular network and cell distribution and profiles less regular in aged individuals. These data were confirmed by scanning electron microscopy, which also showed large areas of the synovial surface devoid of cells and collagen bundles in contact with the joint cavity in aged subjects. Light and transmission electron microscopy confirmed these data and allowed evaluation of the number, distribution, shape, and internal organization of cells as well as the distribution of vessels and the organization of the extracellular matrix in the full thickness of the synovium (down to 2 mm). Particular attention was paid to synovial lining cells, among which three main phenotypes could be recognized: synthetic type (present at all ages and hypertrophied in aged subjects), macrophagelike (increasing with age), and fibroblastlike. Collagen increased with age. Further studies are needed for comprehensive understanding of age-associated changes in the human synovium.
Semin Arthritis Rheum 1992 Jun
PMID:Aging of the human synovium: an in vivo and ex vivo morphological study. 162 86

Collagen arthritis (CA), an autoimmune model of rheumatoid arthritis (RA), has been studied in various animals. However, it has not been studied in an animal with a genetic background relevant to RA. We selected rats from a diabetic-resistant (DR) subline of the diabetic BB rat because they have an autoimmune disease-prone background, but not the immunodeficiencies of the diabetic BB rat, and the third hypervariable region (HVRIII) of the BB RT1.D beta gene appeared to encode a nucleotide sequence of the human HLA DR beta gene, which has been reported to be associated with susceptibility to RA. We synthesized oligonucleotide primers flanking the RT1.D beta HVRIII, cloned polymerase chain reaction-amplified DNA into M13mp18, and confirmed the presence of the susceptibility sequence (SS) (RRRAA) by the dideoxy sequencing method in a colony of DR BB/Wor-UTM rats. When immunized with human type II collagen (CII) in incomplete Freunds adjuvant (IFA), arthritis developed rapidly by day 10 with 100% incidence. Light and electron microscopy revealed an unusually severe and aggressive, bidirectional pattern of cartilage resorption by synovial and subchondral mononuclear and multinucleated inflammatory cells. These findings coincided with a predominant humoral response to the cyanogen bromide (CB) 11 fragment of the human CII molecule by the pathogenic IgG2a isotype. This study provides further support to the role of CA as a relevant RA model, the specific roles of the CB11 fragment as a major site of arthritogenic epitopes, and of antibody mechanisms in the pathogenesis of CA. Furthermore, the identification of an RA SS in an immune response gene of the DR BB rat presents a novel opportunity to determine with an animal model the role of other antigens as well as this SS in RA.
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PMID:Human HLA-DR beta gene hypervariable region homology in the biobreeding BB rat: selection of the diabetic-resistant subline as a rheumatoid arthritis research tool to characterize the immunopathologic response to human type II collagen. 170 52

The relationship between production of IgE and collagen-induced arthritis in mice was examined. Collagen-specific IgE was produced as a consequence of immunization of DBA/1 mice with chicken type II collagen emulsified in CFA. We observed a rise in collagen-specific IgE antibody levels at the onset of CIA clinical and histologic signs in DBA/1 mice. This rise in IgE paralleled that of IgG2a anticollagen antibodies, an isotype implicated in the pathogenesis of CIA by other laboratories. The collagen-specific IgE contained in the plasma of mice with CIA could arm basophils for Ag- (collagen) dependent degranulation. Collagen-specific IgE may thus contribute to CIA by promoting mast cell degranulation in the synovia of susceptible mice immunized with chick type II collagen; but, further work is required to establish such a role for IgE in CIA. However, genetic differences in disease susceptibility could not be accounted for by quantitative differences in collagen-specific IgE production. Further, comparable levels of IgE anticollagen antibodies were observed in animals with active CIA and after spontaneous remission, thereby confirming that the presence of such antibodies is insufficient for disease. Total IgE levels peaked just before spontaneous remission indicating active production of IL-4. IL-4 was administered to animals with CIA to determine if this lymphokine could be involved in the remission process. IL-4 facilitated remission of CIA. Enhanced total IgE production may thus be a marker for activation of Th2 cells that produce lymphokines such as IL-4 and IL-10, factors that may be involved in the spontaneous remission process.
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PMID:Collagen-induced arthritis in mice. Relationship of collagen-specific and total IgE synthesis to disease. 175 95

Articular cartilage contains at least five genetically distinct types of collagen. Types II, IX, and XI are cartilage-specific and are cross-linked together in a copolymeric network that forms the extracellular framework of the tissue. Fibrils of type II collagen provide the basic architecture. Type XI, a quantitatively minor fibril-forming collagen, is probably copolymerized with type II collagen in the matrix. Type IX collagen accounts for approximately 1% of the collagenous protein in adult articular cartilage and its molecules exist in the tissue covalently linked to the surface of type II collagen fibrils. Its suspected functions include regulating fibril diameters and mediating fibril-fibril and fibril-proteoglycan interactions. Stromelysin, a matrix metalloproteinase, was recently shown to degrade type IX collagen. This action may cause the collagen network swelling seen in articular cartilage in early experimental osteoarthritis, (OA). Collagen type X is restricted to the underlying calcified zone of articular cartilage, a zone that exhibits active remodeling in joints with OA. Degradation products of the various cartilage collagens show promise as molecular markers of joint disease.
Semin Arthritis Rheum 1991 Dec
PMID:The collagens of articular cartilage. 179 2


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