Transmission of antibody-induced arthritis is independent of complement component 4 (C4) and the complement receptors 1 and 2 (CD21/35)

Solomon, Samuel; Kolb, Cornelia; Mohanty, Subhasis; Jeisy-Walder, Elvira; Preyer, Rosemarie; Schöllhorn, Volkmar; Illges, Harald

doi:10.1002/1521-4141(200203)32:3<644::aid-immu644>3.0.co;2-5

Cited by 45 publications

(32 citation statements)

References 31 publications

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“…Generation of C4a could therefore account for the mild arthritis found in C3 -/-mice. Mice lacking complement receptor 1 and 2 are not protected against arthritis induced by GPI-specific antibodies [31]. Thus, binding of the C3b and/or C4b fragments to these receptors is unlikely to have any role in arthritis.…”

Section: Discussionmentioning

confidence: 98%

“…Recently, other investigators found that C3 -/-and FB -/-mice but not C4 -/-mice are highly resistant to arthritis induced by transfer of serum containing arthritogenic anti-glucose-6-phosphate isomerase (GPI) antibodies and concluded that the alternative pathway is critical, while the classical pathway is dispensable for development of arthritis [30,31]. GPI is a ubiquitous protein that has been found to precipitate in the synovial lining layer on cartilage surface of mice and shown to be a jointspecific target for arthritogenic antibodies [32].…”

Section: Discussionmentioning

confidence: 99%

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Complement activation by both classical and alternative pathways is critical for the effector phase of arthritis

et al. 2004

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To analyze the role of the classical and alternative pathways of complement activation in the effector phase of arthritis, we have induced arthritis in C3-and factor B (FB)-deficient (C3 -/-and FB -/-) DBA/1J mice using well-defined monoclonal IgG2b and IgG2a antibodies to type II collagen. In control DBA/1J mice, severe swelling of the joints, destruction of cartilage and erosion of bone developed very rapidly with a 100% incidence and a peak on days 7-10. Although 75% of C3 -/-mice developed arthritis, the clinical severity was very mild and the onset was delayed. Severity of arthritis in FB -/-mice ranked intermediate in comparison with C3 -/-and control mice with an incidence of 100%. Immunohistochemical analysis of the inflamed joints demonstrated substantial reduction in macrophage and neutrophilic leukocyte infiltration in both C3 -/-and FB -/-mice, thereby confirming the clinical findings. We conclude that both the classical and the alternative pathways of complement activation are involved in the effector phase of arthritis.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Complement activation by both classical and alternative pathways is critical for the effector phase of arthritis

et al. 2004

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“…Although this is highly suggestive that the disease is driven by CD4 + T cells, it was also found that the development of arthritis required the presence of B lymphocytes Kouskoff et al, 1996). Furthermore, transient arthritis could be transferred by injecting naive mice with serum IgG from arthritic mice in a complement-dependent and FcR-dependent manner, indicating the pathological role played by autoantibodies in this model (Corr and Crain, 2002;Korganow et al, 1999;Solomon et al, 2002). The molecular target of the autoantibodies was identified as glucose-6-phosphate isomerase (GPI), a ubiquitous cytoplasmic enzyme in the context of I-A g7 MHC class II molecules (Matsumoto et al, 1999).…”

Section: (E) Spontaneous Modelsmentioning

confidence: 90%

Animal models of rheumatoid arthritis: How informative are they?

McNamee

Williams

Seed

2015

European Journal of Pharmacology

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Animal models of arthritis are widely used to de-convolute disease pathways and to identify novel drug targets and therapeutic approaches. However, the high attrition rates of drugs in Phase II/III rates means that a relatively small number of drugs reach the market, despite showing efficacy in pre-clinical models. There is also increasing awareness of the ethical issues surrounding the use of animal models of disease and it is timely, therefore, to review the relevance and translatability of animal models of arthritis. In this paper we review the most commonly used animal models in terms of their pathological similarities to human rheumatoid arthritis as well as their response to drug therapy. In general, the ability of animal models to predict efficacy of biologics in man has been good. However, the predictive power of animal models for small molecules has been variable, probably because of differences in the levels of target knockdown achievable in vivo.3

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“…in the disease process in K͞BxN mice has been clearly documented (7)(8)(9); however, the inciting factors that lead to the activation of the autoreactive B and T cells are less clear. T and B cell responses to both foreign and self Ags are primed in lymphoid tissue in close proximity to the source of their Ag (reviewed in ref.…”

mentioning

confidence: 99%

Despite ubiquitous autoantigen expression, arthritogenic autoantibody response initiates in the local lymph node

Mandik-Nayak

Wipke

Shih

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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K͞BxN mice develop an inflammatory joint disease with many features characteristic of rheumatoid arthritis. In this model, the KRN transgenic T cells and nontransgenic B cells both recognize the glycolytic enzyme glucose-6-phosphate-isomerase (GPI) as an autoantigen. Here, we followed the anti-GPI B cell response that naturally arises in K͞BxN mice. The anti-GPI B cell response was robust and arose at the same time as the development of serum anti-GPI autoantibody and joint inflammation. Surprisingly, although GPI was expressed systemically, the anti-GPI B cell response was focused to the lymph nodes (LN) draining the distal joints where arthritis was evident. In lymphotoxin-␤ receptor-Ig-treated mice, which lack LNs, the development of arthritis was completely inhibited up to 5-6 weeks. At later times, some arthritis did develop, but at a significantly reduced level. Thus, in this spontaneous model of autoimmunity, the LNs draining the distal joints are essential for both the inhibition and amplification of the arthritogenic B cell response. These findings imply that the immune physiology of a joint is unique, resulting in a local immune response to a systemic autoantigen.

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Transmission of antibody-induced arthritis is independent of complement component 4 (C4) and the complement receptors 1 and 2 (CD21/35)

Cited by 45 publications

References 31 publications

Complement activation by both classical and alternative pathways is critical for the effector phase of arthritis

Complement activation by both classical and alternative pathways is critical for the effector phase of arthritis

Animal models of rheumatoid arthritis: How informative are they?

Despite ubiquitous autoantigen expression, arthritogenic autoantibody response initiates in the local lymph node

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