Article Text

PDF
AB0083 Blocade of cd28 costimulatory signal reduces autoimmune uveitis in mice model
  1. C. Iwahashi-Shima1,
  2. M. Fujimoto1,
  3. S. Serada1,
  4. T. Naka1
  1. 1Laboratory for Immune Signal, National Institute of Biomedical Innovation, Ibaraki, Japan

Abstract

Background A number of biologic agents have been shown to be effective for the treatment of rheumatoid arthritis (RA). Despite the improvements in the treatment for RA, less progress has been made in the treatment of uveitis associated with RA and other autoimmune diseases. Notably, because immunosuppressive agents including biologics may even worsen the autoimmune comorbid uveitis, the agents to patients with uveitis should be carefully considered. Abatacept, a selective T cell costimulation modulator targeting the CD 28 costimulatory signal, is widely used for the treatment of RA, but its effect on uveitis remains to be determined.

Objectives To determine the effect of the blockade of CD28 costimulatory signal in autoimmune uveitis, mice with experimental autoimmune uveitis (EAU), a preclinical model for uveitis, were treated with various dosages and administration timings of abatacept.

Methods EAU was initiated in C57BL/6J mice by immunization with interphotoreceptor retinoid binding protein (IRBP) in complete Freund’s adjuvant and administration of pertussis toxin. Various dosages (i.e. 5, 50, 500 mg/kg) and timings of administration (simultaneously with the immunization, or at the timing of disease onset) of abatacept were evaluated in this model. Severity of uveitis was assessed using clinical and histological scoring system of EAU. Three weeks after immunization, the bloods were collected to measure the levels of antibody to IRBP.

Results The mice treated with abatacept simultaneously with the immunization exhibited lower clinical scores for uveitis severity compared to the mice without treatment. Administration of 50 or 500 mg/kg of abatacept markedly inhibited uveitis in mice. In contrast, administration of 5mg/kg had only marginal effect. Administration of abatacept at onset (one week after the immunization) also could reduce the severity of uveitis, but was less effective than that administered simultaneously with the immunization. Serum examination revealed that abatacept simultaneously administered with the immunization potently suppressed the anti-IRBP antibody induction, but that administered at onset did not.

Conclusions Blockade of the CD 28 costimulatory signal before the onset resulted in significantly reduced ocular inflammation and anti-IRBP antibody production in mice with autoimmune uveitis. These results suggest that CD28 costimulatory signal plays a critical pro-inflammatory role in the pathogenesis of autoimmune uveitis. Because abatacept administered at onset still had an inhibitory effect on autoimmune uveitis, abatacept may be a potential therapeutic option for eye involvement in RA and other autoimmune diseases.

Disclosure of Interest None Declared

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.