E!6185, THERRA, Karolinska Institutet

Purpose and goal:

We are testing a new therapy idea for rheumatoid arthritis, by using autoantigen-coated nanoparticles, developed by Kira Astakova (Denmark, PI in the present project), that could target anti-citrullinated protein autoantibodies in patients. We will use our experimental models to study the effect of such nanoparticles on autoantibody effects in animal models and also in cell cultures.

Expected results and effects:

1. We can possibly demonstrate that specific autoantibodies can be targeted by autoantigen-coupled nanoparticles in vivo.

2. We can possibly demonstrate that autoantibody levels and effects can be modulated by autoantigen-coupled nanoparticles in the context of rheumatoid arthritis (i.e. a possible treatment opportunity)

3. We can possibly identify non-antigen specific nanoparticle effects on the immune system, which can lead to broader therapeutic applications. Approach and implementation:

We will study the effect of citrullinated nanoparticles (cit-NP) on rheumatoid arthritis patient-derived anti-citrullinated protein autoantibodies in vivo (biodistribution and biological effects, such as bone erosion or arthritis modulation) and we will also analyze a broader immunomodulatory effect of cit-NPs in different immune cell cultures.