The role of Bob1 in rheumatoid arthritis: potential implications for autoimmunity
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ORAL PRESENTATION
Open Access
The role of Bob1 in rheumatoid arthritis: potential implications for autoimmunity Nataliya Yeremenko1*, Tineke Cantaert1, Melissa N van Tok1, Ioana Gofita1, Juan D Canete2, Paul-Peter Tak1, Hergen Spits3, Dominique L Baeten1 From 7th European Workshop on Immune-Mediated Inflammatory Diseases Noordwijk aan Zee, the Netherlands. 28-30 November 2012 Background/purpose Rheumatoid arthritis (RA) is a prototypic autoimmune disease characterized by a prominent humoral autoimmunity. Of particular relevance is the local production of autoantibodies such as rheumatoid factor and anti-citrullinated protein antibodies in the inflamed synovial tissue. The mechanisms underlying break of B cell tolerance and local autoantibody production remains poorly understood. This study was conducted in order to identify cellular and molecular pathways implicated in RA-specific humoral autoimmunity. Methods Synovial tissue samples were obtained by arthroscopy from untreated individuals with RA (n=33) and inflammation matched SpA controls (n=58). Gene expression profiling was performed on tissue samples of patients with established arthritis using 44K Whole Genome Human microarrays (Agilent). Top differentially expressed genes were validated on three independent cohorts by Taqman based RT-qPCR and immunohistochemistry. Collageninduced arthritis (CIA) and Experimental autoimmune encephalomyelitis (EAE) experiments were conducted using Bob1 knockout mice and their littermate controls. Results Microarray screening for genes differentially expressed in the inflamed synovium, the key target of the disease process in RA, revealed a prominent and disease-specific B cell/plasma cell signature with the B cell-specific transcriptional co-activator Bob1 and its transcriptional target BCMA among the most upregulated genes. Validation by 1 Division of Clinical Immunology and Rheumatology and Dept. of Experimental Immunology, Academic Medical Center / University of Amsterdam, Amsterdam, The Netherlands Full list of author information is available at the end of the article
RT-qPCR on two independent cohorts representing early and established arthritis confirmed microarray data and demonstrated elevated expression of Bob1 and BCMA not only in established RA, but also at the early phase of the disease. Quantitative evaluation of immunohistochemical stainings of synovial tissue with monoclonal antibody for Bob1 revealed significant increase in Bob1 positive cells in RA synovium (p
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