Early events in autoimmunity studied by antibody phage display

Abstract

Autoimmune diseases, which affect approximately 2-3% of the world population, are characterized by the occurrence of high titres of autoantibodies. Some of these autoantibodies are disease-specific and their presence is often a valuable diagnostic, and sometimes prognostic, tool for clinicians. For example, autoantibodies directed to citrullinated proteins are almost exclusively present in patients suffering from rheumatoid arthritis, and are therefore regarded as an excellent serological marker for this disease. The question why patients produce autoantibodies is still unsolved. One model that is more and more supported by experimental data, hypothesizes that unusual posttranslational modifications, for example those occurring during cell death, can lead to the generation of neo-epitopes that subsequently can lead to the breaking of immunological tolerance to self-antigens. During the last 15 years the characterization of (auto)antibodies was greatly facilitated by the antibody phage display technology, a sophisticated methodology for the production of recombinant monoclonal antibodies. In this thesis, novel applications of the antibody phage display technology were designed and developed that can be used to gain more insight into the occurrence of autoantibodies and their antigenic targets