Rheumatoid factors

Rheumatoid arthritis (RA) is a relatively common autoimmune disease characterized by chronic inflammation of multiple joints and, in the majority of cases, presence of autoantibodies. The two major autoantibody responses that are implicated in the pathogenesis of RA, and used for diagnosis, are the anti-citrullinated protein antibodies (ACPAs) and rheumatoid factors (RFs). RFs are autoantibodies that bind to other antibodies, specifically to the constant (Fc-) domain of immunoglobulin G (IgG) and can also be present in other diseases and in healthy individuals. The main aim of this thesis was to dissect the RF response and determine whether a better understanding of how and where RFs bind their IgG targets can improve the clinical value of RF assays and provide insight into their pathophysiological role in RA. Using specially designed IgG-Fc targets with selective RF binding RF responses could be classified according to their reactivity pattern. Specific reactivity patterns associated with ACPA-status and risk of developing arthritis in arthralgia patients. Additionally, this thesis describes studies on interactions between ACPAs and RFs, different RF assays, anti-hinge antibodies, and an in-depth analysis of published RF variable region sequences