Autoimmune disease monitoring - a general introduction
In autoimmune disease the immune system reacts against the molecules and cells of the organism itself. The immune reaction leads to inflammation which in turn may lead to organ damage. The immune reactions involve different arms of the immune system in varying degree depending on the disease. Antibodies formed against self molecules, i e autoantibodies are typically found in autoimmune diseases and widely used for diagnosis.
When autoantibodies are bound to the corresponding antigen this leads to immune complex formation. Immune complexes as well as autoantibodies bound to antigens on cells cause complement activation. Antibodies also interact with cells through binding to IgG Fc receptors and importantly, complement and Fc receptors are often both expressed on inflammatory immune cells and mediate the inflammatory response (ref 1).
Thus, complement activation is involved in the pathogenesis of autoimmune disease and particularly in systemic lupus erythematosus (SLE) which may be referred to as the prototype of autoimmune disease. Complement is central in the pathogenesis of SLE where deficiency or consumption of the classical pathway is related not only to immune complexes but also clearance of apoptotic cells, immunological tolerance and cytokine regulation as illustrated in Fig. 1 (ref 2).
Fig. 1. The classical pathway of complement in relation to SLE pathogenesis.
It is important to monitor the autoimmune disease in order to optimize the treatment. Measurement of many different molecules that reflects the activities of the immune system are here of value. Both certain autoantibodies and complement proteins are useful parameters that can be measured in serum samples. Analysis of a large number different autoantibodies with specificity for various disease-related antigens are available at specialized laboratories (ref 3).
In general, complement analysis should initially include functional assays of the three main activation pathways since otherwise many complement aberrations will not be discovered. The functional assays will reveal genetic deficiencies of which some increase the risk for SLE. In addition knowledge of the defects is important for good patient care.
2. Sturfelt G, Truedsson L. Complement in the immunopathogenesis of rheumatic disease. Nature Rev Rheumatol, 8:458-68, 2012.
3. Conrad K, Roggenbuck D, Reinhold D, Sack U. Autoantibody diagnostics in clinical practice. Autoimmun Rev. 11:207-11, 2012.