NEUTROPHIL PHENOTYPING IN PERIODIC AND CHRONIC ARTHRITIS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To assure accurate diagnosis and treatment of autoimmune and autoinflammatory diseases it is necessary to have sensitive and specific means to evaluate disease activity. Biologic agents that selectively inhibit proinflammatory cytokines and leukocytes involved in pathologic responses are currently among the most efficacious means of suppressing disease activity in many of these disorders. However, these agents are not a panacea. Effects are both disease-specific and vary among patients. Unfortunately, clinical tests to assess these soluble mediator levels and cellular mediator activities en masse in patients to support the use and monitor the efficacy of these compounds directly are not available. In our preliminary studies, molecular profiling of a spectrum of inflammatory diseases revealed key regulators and biomarkers of disease activity whose expression changes correlated with clinical response. These results support the hypothesis that molecular screening can be used to develop diagnostic and disease activity monitoring tests that will aid in the optimization and personalization of treatments, resulting in better outcomes for patients. We developed standard operating procedures and lab practices, and obtained Clinical Laboratory Improvement Amendments (CLIA) certification for a prototype disease activity-monitoring test. In the next phase of this project we will address this hypothesis further by performing adequately powered outcome studies to determine the extent to which gene expression and cytokine monitoring can enhance the ability of physicians to more rapidly diagnose and optimize treatment of rheumatoid arthritis patients. In parallel we will continue to develop the technologies necessary for biomarker screening of clinical samples and translation of these results into practicable clinical tests to be performed in our, and similarly equipped, CLIA-certified facilities.