Demonstration of antibodies to collagen and of collagen-anticollagen immune complexes in rheumatoid arthritis synovial fluids

Menzel, J; Steffen, C; Kolarz, G; Eberl, R; Frank, Oliver; Thumb, N

doi:10.1136/ard.35.5.446

Cited by 58 publications

(19 citation statements)

References 5 publications

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“…Several investigators have found antibodies in the sera and synovial fluid of patients with rheumatoid arthritis (RA) and have hypothesized that collagen autoimmunity may be responsible, at least in part, for the observed pathology (16)(17)(18). Antibodies reactive with both native and denatured types I, 11, and I11 collagen have been described in rheumatoid arthritis but the greatest reactivity was found against denatured collagen (19,20).…”

Section: Discussionmentioning

confidence: 99%

Collagen‐induced arthritis in rats

et al. 1979

Arthritis & Rheumatism

133

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When rats were injected intradermally with an oil emulsion of native type I1 collagen, they developed an inflammatory polyarthritis. The incidence and severity of arthritis increased as the amount of collagen injected was increased. Rats 4% weeks old were the most susceptible to the development of arthritis, whereas weanling and older animals were relatively resistant. There was no difference in incidence between males and females. Mononuclear cells from peripheral blood, lymph nodes, and spleen were cultured with type I1 collagen and responded maximally to a collagen concentration of 25 pg/ml. The earliest detectable response was in peripheral blood mononuclear cell cultures obtained 6 to 8 days after immunization. The response of lymph node and spleen cells tended to lag behind that of peripheral blood cells at the earlier time intervals. Antibodies were detected in sera by hemagglutination at 8 days postimmunization. Quantitation of IgM and IgG antibodies by radioimmunoassay showed good correlation with hemagglutination titers and increased binding of collagen by both classes of antibody in arthritic as compared to nonarthritic animals. It is clear that the de- velopment of both humoral and cellular immunity to type I1 collagen is associated with the development of arthritis and may be important in the pathogenesis of this disease.We have previously reported that approximately 40% of rats injected intradermally with an oil emulsion of heterologous or homologous type I1 collagen develop an inflammatory polyarthritis after a latent period of 12 to 20 days. Other types of collagen, cartilage proteoglycans, and denatured type I1 collagen are ineffective in inducing arthritis when injected in an identical manner (1,2). If animals are studied at a time when disease is well developed (21-28 days), arthritic animals have a significantly greater immune response to type I1 collagen than similarly injected nonarthritic rats (3). However, the early sequence of events in development of the immune response and its relation to clinical disease have not been adequately investigated.The present studies were undertaken to d e h e additional factors that might influence the development of collagen-induced arthritis and to evaluate the immunologic response occurring in peripheral blood, lymph nodes, and spleen at regular intervals after injection of type I1 collagen. These studies demonstrate the important influence of the immunizing dose of collagen, route of injection, and the age of the rats on the incidence and severity of arthritis. The early appearance of antibody to type I1 collagen and the quantitation of both IgG and IgM responses reported here suggest that the role of antibody to type I1 collagen in the pathogenesis of arthritis may be more significant than heretofore recognized.

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Section: Discussionmentioning

confidence: 99%

Collagen‐induced arthritis in rats

et al. 1979

Arthritis & Rheumatism

133

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“…These antibodies engage in the formation of complement-binding antigen-antibody complexes which are said to play a major part in the induction and perpetuation of synovial inflammation. In the SF of human patients with RA and OA, anticollagen antibodies (Menzel et al, 1976(Menzel et al, , 1978Stuart et al, 1983;Jasin, 1985) and immune complexes (Cooke, 1980) have been discovered. In RA, these antibodies are produced locally by plasma cells that are located in the synovial tissue (Smiley et al, 1968).…”

Section: Humoral Immunity In Cruciate Diseasementioning

confidence: 99%

Immunopathological mechanisms in dogs with rupture of the cranial cruciate ligament

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et al. 2008

Veterinary Immunology and Immunopathology

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The majority of studies on cranial cruciate ligament (CrCL) disease to date have been carried out on dogs that already sustained a CrCL rupture, which is the end-stage of the disease. Investigations have recently been carried out to study humoral and cellular immunopathological mechanisms in predisposed dogs before clinical rupture of the contralateral CrCL. The cruciate ligaments are mainly composed of collagen type I, and immune responses to collagen have been suggested as a cause of CrCL degradation in dogs. None of these investigations showed evidence that anticollagen type I antibodies alone initiate CrCL damage. However, in predisposed dogs a distinct anticollagen type I antibody gradient was found towards the contralateral stifle joint that eventually sustained a CrCL rupture, suggesting that there was an inflammatory process present in these joints before detectable joint instability occurred. The importance of cellular reactivity to collagen type I in cruciate disease also remains unclear. Peripheral blood mononuclear cell proliferation to collagen type I was very diverse in dogs with cruciate disease whereas some sham operated dogs and healthy dogs tested positive as well. It is not yet determined whether cellular reactivity to collagen type I exists locally in the stifle joints nor whether this could initiate CrCL degradation.Inflammatory processes within the stifle joint can alter the composition of the cruciate ligaments. In animal models of immunemediated synovitis, the mechanical strength of the CrCL is significantly reduced. Immunohistochemical studies on synovial tissues from dogs with rheumatoid arthritis and dogs with cruciate disease revealed that the pathologic features are similar in both joint pathologies and that the differences are mainly quantitative. Joint inflammation induced by biochemical factors such as cytokines has been implied in CrCL degeneration. In several studies, the levels of pro-inflammatory and T helper cytokines were measured in dogs that sustained a CrCL rupture, but the exact role of the various cytokines in the pathogenesis of CrCL disease remains inconclusive. More recently, the levels of the cytokines have been investigated over time in predisposed dogs before and after CrCL rupture. IL-8 expression tended to be higher in stifle joints that will rupture their CrCL during the next 6 months than in those that will not, indicating an inflammatory process in these joints before clinical rupture.

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“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] Among these antibodies, the rheumatoid factor (RF), mainly of the M isotype, is considered to be characteristic of the disease. Thus it is currently used in the diagnosis of RA' "' and constitutes one of the classification criteria proposed by the American Rheumatism Association.…”

Section: Introductionmentioning

confidence: 99%

“…The serum samples are classified according to the increasing immunoreactivity to the B protein. Among the 15 RA serum samples, only one reacts with the B protein alone (1), two of them are positive with only the A and B proteins(2,4) whereas the others react with the three proteins A, B and C(3,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). The serum samples with high titre-like values of 'AKA react with the three proteins according to a continuous pattern which extendsfrom the A to the C protein…”

mentioning

confidence: 99%