Targeting B cells in systemic lupus erythematosus: not just déjà vu all over again

The article by D？rner and colleagues in the current issue of Arthritis Research & Therapy describes an open-label phase I trial of the B cell-specific humanized monoclonal antibody epratuzumab (anti-CD22) in 14 patients with moderately active systemic lupus erythematosus (SLE) (one or more British Isles Lupus Assessment Group (BILAG) Bs in all patients except one) [1]. Clinical improvement was seen in all patients by 7 to 10 weeks after initiation of the 6-week course of four infusions. The infusions were generally well tolerated, and overall no repeated safety signals were seen. Other than a modest and inconsistent fall in B cell counts in peripheral blood, no laboratory parameters were affected, including autoantibodies and complement. These data are supportive of the rationale for the currently active randomized controlled trial of epratuzumab to establish efficacy in SLE.Like the rituximab target (CD20), CD22 is a cell surface protein uniquely expressed on normal B cells from the early stages of development (pre-B) until differentiation into plasma cells [2,3]. Also like rituximab, the initial experience with epratuzumab was with B cell lymphomas, in which it has shown some suggestion of efficacy in uncontrolled series [4]. Beyond these obvious parallels, however, the stories diverge. The CD22 molecule can clearly deliver intracellular signals, either constitutively or after interaction with its ligand, which is an α2,6-sialic acid residue found in many glycoproteins, including IgM and other cell surface proteins. The effect of CD22 signaling is generally, but not entirely, negative or anti-stimulatory, both in terms of Ca2+ flux and protein tyrosine phosphorylation. It modifies signaling through other cell surface molecules, including the B cell receptor (BCR), CD19/21, and CD45. Mice in which the CD22 gene has been disrupted show hyperresponsiveness of B cells to BCR crosslinking, yet paradoxically a deficit in response to T cell-independent antigens. In conju