THU0107 CCL19, a chemokine involved in B-cell trafficking, is related to the decrease of blood memory B-cells and predicts the clinical response to rituximab in rheumatoid arthritis: Results from the smart study
Authors: J. Sellam, S. Rouanet, H. Hendel-Chavez, K. Abbed, B. Combe, J. Sibilia, X. Le Loët, J. Tebib, R. Jourdan, M. Dougados, Y. Taoufik, X. Mariette
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In rheumatoid arthritis (RA), the decrease of peripheral blood memory B-cell may be explained by their migration into the synovium and predicts the response to rituximab (RTX), delineating thus a B-cell-driven RA subtype. <h3>Objectives</h3> We aimed to investigate whether the serum levels of chemokines involved in B-cell trafficking are correlated with the decrease of blood memory B-cells before RTX and may predict the clinical response to RTX in RA. <h3>Methods</h3> 208 RA patients all treated with methotrexate but refractory or intolerant (n=194) or with contra-indication (n=14) to anti-TNF have been included in the RTX retreatment dose “SMART” study. All received a 1st course of RTX (1g on days 1 and 15) and EULAR response was evaluated at week 24 (W24). Before the 1st RTX infusion, a blood sample was obtained to assess CD19 B-cells subsets by flow cytometry using CD27 and IgD stainings, serum B-cell activation biomarkers (rheumatoid factor [RF], anti-CCP, free light chains [FLC], IgG, IgA, IgM levels and BAFF) and serum chemokines (CCL19, CXC12, CXCL13) by ELISA. We aimed to determine whether serum chemokines levels were correlated with memory B-cells and/or serum B-cell biomarkers (Spaerman correlation) and whether they may predict subsequent EULAR response at W24 in univariate and multivariate analyses (logistic regression). <h3>Results</h3> Among the 208 patients (age =56±11 years, 85% of women, initial DAS28-CRP =5.8±0.9), 149 (72%) were responders (44 good [21%] and 105 partial [51%] responders). The 3 chemokines levels were correlated positively with several serum B-cell biomarkers and inversely with blood CD27+ memory B-cell and especially the CD27+ IgD- switched subtype (Table). Univariate analysis showed that logarithm-transformed CCL19 level (logCCL19) was associated to the EULAR response at week 24 (odds ratio [OR]=1.432; 95%confidence interval [95%CI]: 1.08-1.90; p=0.01). In multivariate analysis, after adjustment on DAS28 and memory B-cell frequency, logCCL19 predicted the response to rituximab at week 24 (OR=1.48; 95%CI: 1.06-2.06; p=0.02). However, this association did not persist after adjusting for RF or anti-CCP positivity. Conversely, CXC12 and CXCL13 levels were not predictive of response. <h3>Conclusions</h3> An increased serum level of the CCL19, CXCL12 and CXCL13 chemokines was related to the decrease of blood memory CD27+ B-cells in RA before RTX and may represent an additional feature of a B-cell-driven RA subtype. We demonstrate for the first time that serum CCL19 may predict the clinical response to RTX in RA, independently of B-cell subsets disturbances. <h3>Disclosure of Interest</h3> J. Sellam: None Declared, S. Rouanet Employee of: Roche France, H. Hendel-Chavez: None Declared, K. Abbed: None Declared, B. Combe: None Declared, J. Sibilia: None Declared, X. Le Loët: None Declared, J. Tebib: None Declared, R. Jourdan Employee of: Roche France, M. Dougados: None Declared, Y. Taoufik: None Declared, X. Mariette: None Declared