Substantial advances have been made in our understanding of the immunologic and genetic mechanisms that contribute to the pathogenesis of rheumatoid arthritis (RA). Although traditional disease modifying anti- rheumatic drugs (DMARDS) are effective, over 65-75% of patients do not respond to these therapies. Even with combination with anti-TNF therapy, no more than 50% of patients achieve remission. As many as 50% of anti-TNF refractory patients are also inadequate responders to second-line therapies. More strikingly, 24% of RA patients do not even demonstrate a minimal level of response to any therapy. Thus, identifying patients that may respond to anti-TNF therapy or other biologic therapies would greatly benefit the patient medically and economically. However, there is a lack of biomarkers in RA to identify the most effective therapy for a given patient due to the fact that few medical practices in the United States examine synovial tissue, as this requires a biopsy, which may not be medically necessary. Over the past several years ultrasound technology has become an important tool in the practice of rheumatology in the United States. Recently, minimally invasive ultrasound guided synovial biopsies have shown great promise, as there are minimal to no complications associated with the procedure. While this procedure is widely accepted throughout Europe, it has not become a common practice for rheumatologists in the United States. To address this unmet need in the United States, we have assembled a consortium of leading academic rheumatology groups which include the University of Alabama Birmingham, Columbia University, Mayo Clinic, Washington University, University of Michigan, and Northwestern University to form the RhEumatoid Arthritis SynOvial tissue Network (REASON). Thus, we will be creating a new generation of rheumatologists in the United States who will perform minimally invasive ultrasound guided synovial biopsies that is critical for obtaining of synovial tissue from patients at all phases of RA (early, established, DMARD or biologic inadequate response). These tissues will be analyzed by researchers at REASON technology sites who will use this material for translational studies to identify novel pathways and potential biomarkers that might predict therapeutic response.

Public Health Relevance

Incomplete understanding of synovial pathophysiology is due in large part to the fact that obtaining synovial tissue biopsy is not required for diagnosis and thus is not clinically indicated. We have created (REASON) to perform minimally invasive ultrasound guided synovial biopsies on RA patients with active disease. The tissues and blood will be examined using cutting edge techniques to identify potential biomarkers for therapeutic response.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Exploratory/Developmental Cooperative Agreement Phase I (UH2)
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Special Emphasis Panel (ZAR1-KM (M1))
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Serrate-Sztein, Susana
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Northwestern University at Chicago
Internal Medicine/Medicine
Schools of Medicine
United States
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Mandelin 2nd, Arthur M; Homan, Philip J; Shaffer, Alexander M et al. (2018) Transcriptional Profiling of Synovial Macrophages Using Minimally Invasive Ultrasound-Guided Synovial Biopsies in Rheumatoid Arthritis. Arthritis Rheumatol 70:841-854
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Cuda, Carla M; Pope, Richard M; Perlman, Harris (2016) The inflammatory role of phagocyte apoptotic pathways in rheumatic diseases. Nat Rev Rheumatol 12:543-58