Background Antibody Fab fragments (Fabs) maintain the ability to bind to specific antigens but lack the binding site for complement as well as the site for binding to receptors on immune and inflammatory cells that play a critical role in autoimmune diseases including collagen-induced arthritis (CIA) in mice. Therefore, CIA might be regulated by type II collagen (CII)-specific antibody Fabs.

Objectives The present study was performed to investigate the effect of Fabs of arthritogenic CII-specific IgG2b (C2B-9 and C2B-14) monoclonal antibodies (mAb) on CIA and to define the mechanism underlying the suppression of the autoimmune joint inflammation by the Fabs.

Methods To induce CIA, DBA/1J mice were immunized by subcutaneous injections of CII plus CFA into the base of the tail on days 0 and 21. Hybridomas producing C2B-9 and C2B-14 were established by fusing anti-CII antibody-producing spleen cells and myeloma cells. C2B-9 and C2B-14 Fabs were prepared by the digestion of the CII-specific mAbs with papain and injected i.p. on days -1 and 3. The effect of the Fabs on CIA was evaluated clinically, serologically, and histologically.

Results Treatment with C2B-9 or C2B-14 Fabs alone failed to suppress CIA. In contrast, the combination of C2B-9 and C2B-14 Fabs significantly suppressed both the incidence and the severity of CIA. The suppression of CIA by the Fabs was associated with a decrease in CII-specific IgG in serum. Histologically, proliferation of synovium, infiltration of inflammatory cells including mononuclear cells, and destruction of cartilage and subchondral bone were diminished in C2B-9 and C2B-14 Fab-treated animals. In vitro studies revealed that the capture of CII by O2B-9 or O2B-14 Fabs prevented the subsequent binding of intact anti-CII polyclonal antibodies to the captured CII.

Conclusions These results suggest that autoimmune inflammatory diseases such as rheumatoid arthritis might be specifically regulated by pathogenic mAb Fabs via the interference with autoantigen-intact autoantibody interaction by the fragments, resulting in the suppression of complement and immune/inflammatory cell activation.

References

1. Yoshino, S., et al., Br. J. Pharmacol., 161:1351-1360, 2010.

2. Koobkokkruad, T., and Yoshino, S., et al., J. Inflamm., 8:31-37,2011.

3. Yoshino, S., et al., Immunol., 141:617-627, 2014.

Disclosure of Interest None declared