43 Inflamed joints share dominant B-cell clones Introduction Adaptive immune cells are key players in the pathogenesis of rheumatoid arthritis (RA) [1–8]. The immune response in RA is encoded by rearranged receptors expressed by clones of T and B lymphocytes, plasmablasts and plasma cells. Targeting the adaptive immune response using novel targeted therapies, also known as biologics, for instance with abatacept (CTLA4-Ig) or rituximab has been proven to be of clinical benefit in RA patients [6,9]. Despite these important developments in the treatment of RA, there is still no cure for RA patients available. Only 60% of RA treatments are effective, and often merely induce a partial clinical response [10]. Thus, there is a clear need to develop novel, targeted, more effective therapies. Recent studies showed that a common T-cell receptor signature can be found in the synovial tissue (ST) of RA patients [11]. This suggests that antigen- and/or receptor- specific therapies targeting a limited set of T-cell clones in individual patients may be feasible in RA. Another key player of the adaptive immune system, the B-cell, also appears to be of great relevance in RA as it is an antibody-driven disease in which anti-cyclic citrullinated peptide antibodies (ACPA) and IgM- rheumatoid factor (IgMRF) play a key role. Consequently, antigen receptor specific targeting of B-cells might even be more attractive. However, to assess whether B-cells might indeed constitute an interesting target for antigen receptor specific therapy, more information on the distribution of B- cell clones over different joints in the same patient is required. This study was designed to investigate the distribution of the B-cell receptor (BCR) repertoire using a high-throughput quantitative approach in a unique cohort of 11 RA patients, in which synovial tissue (ST) biopsies were taken from multiple locations within the same joint, in another (contralateral) joint, as well as synovial fluid (SF) and peripheral blood (PB) samples. Using this method, we aimed to answer the following three questions: 1) Do different B-cell clones dominate the BCR repertoire at different locations within one single inflamed joint? 2) Are BCR repertoires in different inflamed joints dominated by the same BCR-clones? 3) Do the same dominant BCRclones reside in different compartments, such as ST, SF and PB at the same time? Materials and methods Patients Eleven RA patients meeting the 2010 ACR/EULAR Classification Criteria for RA with active disease (disease activity score evaluated in 28 joints (DAS28) >3.2) were included [12]. Details of the included patients are described earlier [11]. All were autoanti3
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