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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
  1. J. Sellam1,
  2. S. Rouanet2,
  3. H. Hendel-Chavez3,
  4. K. Abbed3,
  5. B. Combe4,
  6. J. Sibilia5,
  7. X. Le Loët6,
  8. J. Tebib7,
  9. R. Jourdan8,
  10. M. Dougados9,
  11. Y. Taoufik3,
  12. X. Mariette10
  1. 1Rheumatology Department, Saint-Antoine Hospital, Ap-Hp, Pierre et Marie Curie University, Paris
  2. 2Biostatistics, Roche France, Neuilly/Seine
  3. 3Biological immunology, Bicêtre Hospital, Ap-Hp, Université Paris-Sud 11, Kremlin Bicêtre
  4. 4Immuno-Rheumatology, Lapeyronie University Hospital, Montpellier I University, UMR5535, Montpellier
  5. 5Rheumatology Department, Ea 3432, Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg
  6. 6Rheumatology Department, Rouen University Hospital, INSERM U905, Rouen
  7. 7Rheumatology Department, Centre Hospitalier Lyon-Sud, Pierre-Bénite
  8. 8Medical Department, Roche France, Neuilly/Seine
  9. 9Rheumatology B Department, Paris-Descartes University, Upres-Ea 4058, Cochin Hospital, Ap-Hp, Paris
  10. 10Rheumatology Department, INSERM U1012, Bicêtre Hospital, Ap-Hp, Université Paris-Sud 11, Kremlin Bicêtre, France

Abstract

Background 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.

Objectives 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.

Methods 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).

Results 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.

Conclusions 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.

Disclosure of Interest 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

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