**4. Conclusion**

Autoimmune diseases including RA are not only rare but also difficult to treat. In the clinical field, biological agents have emerged as attractive therapeutic options for these diseases, because of their rapid and/or dramatic effectiveness to intractable diseases. However, biological agents are expensive and their usage is occasionally accompanied with severe adverse effects such as immunosuppression and fatal infection. To maximize the therapeutic potential and to minimize the adverse effects of biological agents, novel biomarkers are required for the selection of agents, monitoring of the disease activity and therapeutic efficacy or differential diagnosis of infection. In this respect, LRG we identified from iTRAQ analysis is a candidate of novel biomarkers useful for clinical practice of biological agents since it correlates with disease activity and therapeutic effectiveness of biological agents. In addition, the application of iTRAQ analysis, the novel quantitative proteomic approach, is useful for the identification of new serological biomarkers in patients with autoimmune diseases. Further studies using this approach may lead to the development of additional new biomarkers and may help to clarify the pathogenesis and identify therapeutic targets in autoimmune diseases.

#### **5. References**


previous reports, it seems that LRG is not a unique biomarker in autoimmune disease but rather is a generalized inflammatory biomarker, because serum LRG levels are reported to be increased in patients with bacterial infection and several types of cancers. Nevertheless, serum LRG satisfies the condition of an inflammatory biomarker in the point that its concentration is high at diagnosis, correlated well with disease activity and is a possible predictor of the responsiveness to biological agents. For these reasons, serum LRG is a novel inflammatory biomarker potentially surrogate for CRP. Further studies are in progress in our laboratory to determine the pathophysiological function of LRG and the clinical benefit

Autoimmune diseases including RA are not only rare but also difficult to treat. In the clinical field, biological agents have emerged as attractive therapeutic options for these diseases, because of their rapid and/or dramatic effectiveness to intractable diseases. However, biological agents are expensive and their usage is occasionally accompanied with severe adverse effects such as immunosuppression and fatal infection. To maximize the therapeutic potential and to minimize the adverse effects of biological agents, novel biomarkers are required for the selection of agents, monitoring of the disease activity and therapeutic efficacy or differential diagnosis of infection. In this respect, LRG we identified from iTRAQ analysis is a candidate of novel biomarkers useful for clinical practice of biological agents since it correlates with disease activity and therapeutic effectiveness of biological agents. In addition, the application of iTRAQ analysis, the novel quantitative proteomic approach, is useful for the identification of new serological biomarkers in patients with autoimmune diseases. Further studies using this approach may lead to the development of additional new biomarkers and may help to clarify the pathogenesis and

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**Part 3** 

**Therapeutic Interventions** 

