Journal of IiME Volume 8 Issue 1 been shown that the soluble molecule can positively control IgE synthesis (30, 31). Therefore, sCD23 levels would serve as a potential biomarker of memory cell formation, the detection of which in peripheral circulation is predictive of clinical relapse. Experimental plan: RA: As the relationship between B cell kinetics and relapse after RTX is highly variable between patients, we identified 4 key time points in each cycle for analysis: Baseline (pre-RTX in each cycle); when B-cell depleted (CD19+Breturn (CD19+B(ΔDAS28>1.2). SLE: The relationship between B cell return and disease flare is also highly variable in these patients and the kinetics of the clinical response differs from RA. We will therefore use length of time to flare after treatment either (<6 months) and between 612 months to determine efficacy of treatment, as we have previously described (32, 33). Therefore we will include samples collected at baseline (prior to RTX) and at 3, 6, 9 and 12 month intervals. Determination of disease activity and flare will be assessed by BILAG2004(34). Protocol Patients: Stored serum samples are available from patients treated with RTX over the last 12 years (from our cohorts of >250 patients with RA; 100 patients with SLE). Clinical data will be collected retrospectively and samples from the same patients tested concurrently. Levels of soluble CD23 will be measured using ELISA (R and D systems). Isotypes of Rheumatoid factors (RhF) and anti-cyclic citrullinated peptides (CCP) will be measured using ELISA kits (from Axis Sheild, Dundee, UK). We aim to include samples from 30 patients with RA and 20 with SLE. Differences between time points will be assessed following log transformation and T-test with significance level set at 1%. Correlations between variables (sCD23, autoantibodies) will be by linear regression. Multivariate analysis will be used to determine relationships between serum sCD23 levels, levels of autoantibodies and duration of clinical response, assessed by EULAR response criteria for RA patients; flare< or ≥ 6 months; and SLE responder index for SLE. References 1. Maloney DG, Grillo-Lopez AJ, White CA, Bodkin D, Schilder RJ, Neidhart JA, et al. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy May 2014 in patients with relapsed low-grade non-Hodgkin's lymphoma. Blood. 1997;90(6):2188-95. 2. Khan A, Scott D. Rituximab after methotrexate failure in rheumatoid arthritis: evaluation of the SERENE trial. Expert opinion on biological therapy. 2011;11(11):1515-8. 3. Leandro MJ, Edwards JC, Cambridge G, -cell Ehrenstein MR, Isenberg DA. An open study of B lymphocyte depletion in systemic lupus erythematosus. Arthritis and rheumatism. 2002;46(10):2673-7. 4. Diaz-Lagares C, Croca S, Sangle S, Vital EM, Catapano F, Martinez-Berriotxoa A, et al. Efficacy of rituximab in 164 patients with biopsy-proven lupus nephritis: pooled data from European cohorts. Autoimmunity reviews. 2012;11(5):357-64. 5. Isenberg DA. Rituximab-it was the best of times, it was the worst of times. Autoimmunity reviews. 2012;11(11):790-1. 6. Popa C, Leandro MJ, Cambridge G, Edwards JC. Repeated B lymphocyte depletion with rituximab in rheumatoid arthritis over 7 yrs. Rheumatology (Oxford). 2007;46:626-30. 7. Anolik JH, Barnard J, Owen T, Zheng B, Kemshetti S, Looney RJ, et al. Delayed memory B cell recovery in peripheral blood and lymphoid tissue in systemic lupus erythematosus after B cell depletion therapy. Arthritis and rheumatism. 2007;56(9):3044-56. 8. Edwards JC, Cambridge G. Sustained improvement in rheumatoid arthritis following a protocol designed to deplete B lymphocytes. Rheumatology (Oxford). 2001;40(2):205-11. 9. Vital EM, Rawstron AC, Dass S, Henshaw K, Madden J, Emery P, et al. Reduced-dose rituximab in rheumatoid arthritis: efficacy depends on degree of B cell depletion. Arthritis and rheumatism. 2011;63(3):603-8. 10. Vital EM, Dass S, Buch MH, Henshaw K, Pease CT, Martin MF, et al. B cell biomarkers of rituximab responses in systemic lupus erythematosus. Arthritis and rheumatism. 2011;63(10):3038-47. 11. Dass S, Rawstron AC, Vital EM, Henshaw K, McGonagle D, Emery P. Highly sensitive B cell analysis predicts response to rituximab therapy in rheumatoid arthritis. Arthritis and rheumatism. 2008;58(10):2993-9. 12. Nakou M, Katsikas G, Sidiropoulos P, Bertsias G, Papadimitraki E, Raptopoulou A, et al. Rituximab therapy reduces activated B cells in both the peripheral blood and bone marrow of patients with rheumatoid arthritis: depletion of memory B cells correlates with clinical response. Arthritis research & therapy. 2009;11(4):R131. Invest in ME (Charity Nr. 1114035) www.investinme.org Page 15 of 52
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