Neutralization of AntiCitrullinated Protein Antibodies in Rheumatoid Arthritis – A Way to Go?

Anticitrullinated protein antibodies (ACPAs) constitute a class of autoantibodies found in 60-70% of patients with rheumatoid arthritis (RA). The most common test for ACPA positivity is based on the occurrence of antibodies that bind to circular citrullinated peptides, so-called CCP, some of which are derived from endogenously citrullinated proteins, like filaggrin. Several lines of evidence suggest that these autoantibodies may confer pathological reactions. They appear years before onset of clinical disease and are associated with worse prognosis and a more erosive disease. Their presence correlates with the most prominent genetic risk factors for RA development, and they were recently described to mediate relevant biological functions such as activation of complement system and induction of osteoclastogenesis. The development of new drugs that specifically target these autoantibodies is an appealing and novel approach. Herein, we briefly review the autoimmune condition of RA, characterized by the presence of ACPA, and we describe how the neutralization of autoantibodies might become a novel pharmacological principle.