Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Effect of Rituximab Treatment On Cytokine/Chemokine Profile in Patients with Primary Sjgrens Syndrome
Pollard, R.P.E., Abdulahad, W.H., Meijer, J.M., Huitema, M.G., Spijkervet, F.K.L., Kallenberg, C.G.M., Vissink, A.
To assess the effect of rituximab (anti-CD20) treatment on the cytokines/chemokines profile in patients with primary Sjögren's syndrome (pSS).
In a randomised double-blinded placebo-controlled trial patients were treated on days 1 and 15 with either rituximab (n= 20) or placebo (n= 10). Fresh blood samples were collected at various time points (before, 5, 12, 36 and 48 weeks following treatment). In addition, age- and sex-matched blood samples were collected from healthy controls (n=10). B and T-cells were examined by four-color cytometry. A multiplex-25 bead array cytokine assay was used enabling simultaneous measurement of (1) proinflammatory cytokines (GM-CSF, IL-1b, IL-1RA, IL-6, IL-8, TNF-a); (2) Th1/Th2 distinguishing cytokines (IFN-g, IL-2, IL-2R, IL-4, IL-5, IL-10); (3) nonspecific acting cytokines (IFN-a, IL-7, IL-12p40/p70, IL-13, IL-15, IL-17); and (4) chemokines (Eotaxin, IP-10, MCP-1, MIP-1a, MIP-1b, MIG, RANTES).
Depletion of B-cells was observed in the rituximab treated group after first infusion, while B-cell levels remained unchanged after placebo treatment. The B-cells reappeared in the rituximab treated group within 24 to 48 weeks after treatment. Regarding CD4+ and CD8+ T cells no changes were observed between the rituximab and placebo treated patients at all time points. When compared to healthy controls, except for IL-8 and IFN- g, an increase was seen in the levels of the other cytokines at baseline. After rituximab treatment, a decrease and subsequent (partial) recovery within 24 to 48 weeks was observed for IL-1b, IL-1RA, IL-2R, IL-4, IL-5, IL12, IL-15, IL-17, TNF-a, GM-CSF, MIP-1a, MIP-1b, MIG, Eotaxin, MCP-1. As compared to placebo, the most striking early decrease was observed in IL-10 levels.
These preliminary data show a variation in cytokine/chemokine profile before and after rituximab therapy in conjunction with a depletion and reappearance of B-cells. Related to the observed changes in cytokine profiles, specific cytokines are noted that may play a role in pathogenesis of pSS. This observation will be correlated with clinical data. Extended data are in progress.
To cite this abstract, please use the following information:
Pollard, R.P.E., Abdulahad, W.H., Meijer, J.M., Huitema, M.G., Spijkervet, F.K.L., Kallenberg, C.G.M., et al; Effect of Rituximab Treatment On Cytokine/Chemokine Profile in Patients with Primary Sjgrens Syndrome [abstract]. Arthritis Rheum 2009;60 Suppl 10 :505