Application of Novel Quantitative Proteomic Technologies to Identify New Serological Biomarkers in Autoimmune Diseases

Autoimmune diseases comprise a wide variety of systemic or organ-specific inflammatory diseases, characterized by aberrant activation of immune cells that target self tissues due to misrecognizing tissue-derived proteins as foreign antigens (Hueber and Robinson, 2006; Prince, 2005). The prevalence of autoimmune diseases is approximately 2,000 ~ 3,000 per 100,000, although the prevalence varies depending on the diseases, ethnic groups and regions (Prieto and Grau, 2010). The etiology and exact pathogenesis of autoimmune diseases remain poorly understood. However, both genetic factors and environmental triggers are profoundly involved in the pathogenesis of autoimmune diseases. Notably, clinical manifestations of autoimmune disease may be different among patients, even though they have the same diagnosis, depending on the affected organs of each patient. Therefore, careful evaluation of the clinical manifestations combined with the examination of laboratory tests is required for proper diagnosis of autoimmune diseases and subsequent monitoring of the disease activity during therapy. In addition, therapeutic choices for these diseases have been limited so far and conventional therapeutics include non-steroidal antiinflammatory drugs (NSAID), glucocorticoids, cytotoxic drugs and disease modifying anti rheumatoid drugs (DMARDs). For these reasons, autoimmune diseases have been considered to be intractable and the goal of the treatment is to control disease activity rather than to achieve remission or cure. Recently, however, the advent of biological agents has led to the marked improvement in the treatment of rheumatoid arthritis (RA) and other inflammatory autoimmune diseases. These agents greatly contribute to improve health-related quality or daily life of patients with autoimmune diseases (Han et al., 2007; Keystone et al., 2008; Laas et al., 2009; Strand and Singh, 2007). Nevertheless, biological agents are not effective for all patients with autoimmune diseases and current biomarkers are not helpful to select an effective biological agent for individual patients. In addition, conventional inflammatory biomarkers are often inadequate to evaluate the disease activity in patients treated with biological agents. Thus, there is a growing need for the development of new biomarkers that can predict individual treatment response before starting biological therapy and evaluate the disease activity and therapeutic efficacy during therapy. In this chapter, we first outline the clinical usage and