Anti Citrullinated Protein Antibodies and Mechanism of Action of Common Disease Modifying Drugs - Insights in Pathomechanisms of Autoimmunity

Georg      Pongratz; Martin      Fleck

Abstract

The increasing understanding of autoimmune mechanisms continuously leads to new therapeutic targets and development of novel diagnostic tools in rheumatology. On the other hand, an improved comprehension of mechanisms of action of many drugs and the daily utilization in rheumatology leads to a better understanding of the underlying autoimmune processes. An example for the latter is Bcell depletion using anti-CD20 antibodies, which leads to the concept of B cells not only playing a role as antibody secreting cells but also as important cellular components of autoimmune processes, acting as antigen presenting and cytokine producing cells. Another example is the conventional disease modifying anti-rheumatic drug methotrexate, which has also been used successfully in the clinic first and then, while trying to understand its mechanism of action, led to knew insights in autoimmune mechanisms e.g. revealing the strong anti-inflammatory potential of adenosine. But not only the mechanism of action of different drugs, but also the identification of antibodies against citrullinated proteins (ACPA) as a valuable diagnostic tool resulted in novel concepts regarding the pathophysiology of rheumatoid arthritis. The following review first explains the value of ACPA in the diagnosis of rheumatoid arthritis (RA) and then summarizes the application and mechanism of action of several important substances used in the management of autoimmune disorders. Based on these insights, the authors explain their understanding of the autoimmune process as a continuous repeat of autoantigen presentation – autoreactive effector cell activation – destruction of tissue – liberation of new autoantigens – and again autoantigen presentation, which closes the vicious circle.

Keywords: Autoimmune diseases, pathogenesis, therapeutic mechanisms, rheumatology, B cells, anti-CD20, antibodies, methotrexate, cytokine producing cells, ACPA, rheumatoid arthritis (RA).