Uthors critically revised the manuscript, and all authors read and approved the final manuscript. Acknowledgments This study was supported by grants from Collaborative Research Center 650 (SFB 650 project A14) of Charit- Universit smedizin Berlin and in part by an unrestricted analysis grant by UCB Celltech, Slough, UK. The monoclonal antibody epratuzumab and F(ab)2 fragments have been kindly provided by UCB Celltech, Slough, UK. Author details Division Medicine/Rheumatology and Clinical Immunology, CharitUniversity Medicine Berlin, CC12, CharitBerlin, Charit latz 01, 10098 Berlin, Germany. 2German Rheumatism Study Center Berlin (DRFZ), Leibniz Institute, Berlin, Germany. 3UCB Celltech, Slough, UK.axis largely intact. This regulatory dichotomy appears to become important to clarify the distinct effects when targeting CD22 that’s closely linked to downstream functions of BCR activation. It need to be emphasized that the influence of epratuzumab on IL-6, TNF- and IL-10 production was comparable among SLE B cells and controls, but that the ratios of IL-10 to TNF- and IL-10 to IL-6 had been substantially different in SLE upon BCR-TLR9 stimulation. Even though a prospective influence of non-B cells contributing for the in vitro cytokine production cannot be completely excluded, the imply B cell purity of 98.five 2.two with only two samples with eight.two and 5.6 non-B cells didn’t most likely lead to a substantial difference inside the influence of the mAb against CD22, due to the fact this bindingFleischer et al. Arthritis Study Therapy (2015) 17:Page 7 ofReceived: 27 January 2015 Accepted: 16 JuneReferences 1. Anolik JH. B cell biology and dysfunction in SLE. Bull NYU Hosp Jt Dis. 2007;65:182. two. D ner T, Jacobi AM, Lee J, Lipsky PE. Abnormalities of B cell subsets in patients with systemic lupus erythematosus. J Immunol Approaches. 2011;363:1877. three. Carnahan J, Wang P, Kendall R, Chen C, Hu S, Boone T, et al. Epratuzumab, a humanized monoclonal antibody targeting CD22: characterization of in vitro properties. Clin Cancer Res. 2003;9:3982S0S. four. Jacobi AM, Goldenberg DM, Hiepe F, Radbruch A, Burmester GR, Dorner T. Differential effects of epratuzumab on peripheral blood B cells of individuals with systemic lupus erythematosus versus regular controls. Ann Rheum Dis. 2008;67:450. five. Daridon C, Blassfeld D, Reiter K, Mei HE, Giesecke C, Goldenberg DM, et al. Epratuzumab targeting of CD22 impacts adhesion molecule expression and migration of B-cells in systemic lupus erythematosus. Arthritis Res Ther. 2010;12:R204. 6. Sieger N, Fleischer SJ, Mei HE, Reiter K, Shock A, Burmester GR, et al.Tachysterol 3 structure CD22 ligation inhibits downstream B cell receptor signaling and Ca2+ flux upon activation.154775-43-6 Chemical name Arthritis Rheum.PMID:24013184 2013;65:770. 7. Macauley MS, Crocker PR, Paulson JC. Siglec-mediated regulation of immune cell function in disease. Nat Rev Immunol. 2014;14:6536. eight. Fillatreau S. Cytokine-producing B cells as regulators of pathogenic and protective immune responses. Ann Rheum Dis. 2013;72:ii80. 9. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40:1725. ten. Petri M, Kim MY, Kalunian KC, Grossman J, Hahn BH, Sammaritano LR, et al. Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med. 2005;353:2550. 11. Mei HE, Yoshida T, Sime W, Hiepe F, Thiele K, Manz RA, et al. Blood-borne human plasma cells in steady state are derived from mucosal immune responses. Blood. 2009;11.