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SAT0040 Arthritis induced by newly developed anti-type II collagen mabs associated with antigen affinity
  1. S. Yoshino
  1. Pharmacology, Kobe Pharmaceutical University, Kobe, Japan

Abstract

Background Polyclonal antibodies or a combination of 4 or 5 mAbs specific for type II collagen (CII) induce severe arthritis in mice (CAIA model). The induction of CAIA is associated with antigen affinity and complement activation. However, it is not completely clear that an anti-CII mAb itself or a combination of only 2 anti-CII mAbs is albe to induce severe arthritis. It is also not well understood whether the binding ability of anti-CII mAbs to CII is more important for the induction of CAIA than complement activation by the immune complexes.

Objectives To establish new hybrydoma cells producing anti-CII mAbs, to test the ability of an anti-CII mAb alone or a combination of only two anti-CII mAbs to induce arthritis, and to investigate the association of the arthritogenicity of anti-CII mAbs with antigen affinity or complement activation.

Methods DBA/1J mice were immunized with chicken CII and then the spleen cells were fused with myeloma cells before cloning cells producing anti-CII mAbs and determining their isotypes. An anti-CII mAb alone or a combination of two anti-CII mAbs that crossreacted with mouse CII were i.p. injected to attempt to induce arthritis. The binding ability of anti-CII mAbs to CII and complement activation were analyzed by ELISA in vitro.

Results A number of hybydoma cells producing varying isotypes of anti-CII mAbs including IgG1, IgG2a, IgG2b, IgG3, IgM, and IgD were established. Two anti-CII IgG2b mAbs (C2B-9 and C2B-14) had markedly strong affinity to mouse CII. Two anti-CII IgG2a mAbs showed either moderate (C2A-7) or weak (C2A-12) affinity to the collagen. C2B-14 and C2A-12 showed more marked complement activation than C2B-9. I.p. injection of C2B-9 or C2B-14 alone induced weak arthritis while a combination of C2B-9 and C2B-14 caused severe joint inflammation. The animals injected i.p. with a combination of C2B-14 and C2A-12 had weak arthritis.

Conclusions An anti-CII mAb alone is able to induce arthritis. A combination of two anti-CII mAbs is much more effective in causing severe joint inflammation. Induction of arthritis appears to be more importantly associated with the intensity of antigen affinity than complement activation.

  1. Hutamekalin P., Saito, T., Yamaki, K., Mizutani, N., Brand, D.D., Waritani, T., Terato, K., Yoshino, S.: Collagen antibody-induced arthritis in mice: Development of a new arthritogenic cocktail of monoclonal anti-type II collagen antibodies. J. Immunol. Methods, 34:49-55, 2009.

Disclosure of Interest None Declared

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