Epratuzumab (humanised anti-CD22 antibody) in primary Sj？gren's syndrome: an open-label phase I/II study

Primary Sj？gren's syndrome (pSS) is a systemic autoimmune disease with a population prevalence of approximately 0.5% [1]. The lymphoid infiltrates within the inflamed tissues contain ectopic germinal center-like structures in 20% of patients [2]. These structures consist of T- and B-cell aggregates containing proliferating lymphocytes, follicular, dendritic, and activated endothelial cells [3]. B-cell homeostasis is disturbed in pSS, with diminished frequencies and absolute numbers of peripheral CD27+ memory B cells. However, the infiltrating B cells are mainly CD27+ memory B cells and CD27high plasma cells [4-6]. This altered B-cell subtype recirculation from inflamed tissue was confirmed recently by Hansen et al. [7]. Thus, although pSS is considered to be a T-cell-mediated disease, high levels of B-cell autoreactivity have been associated with high disease activity, the development of systemic complications, and an increased risk of development of B-cell lymphoma [8].This has led to anti-B-cell monoclonal antibody immunotherapy emerging as a promising new treatment modality in pSS and autoimmune disorders [9]. The use of rituximab, a chimeric anti-CD20 antibody, has been reported in small studies and case reports of SS patients with or without associated lymphoma [10-13]. However, serum sickness-like diseases seem to occur in approximately 20% of patients treated with this chimeric antibody [11] and may be of major clinical concern in subjects with a hyperactive immune system.CD22 is a 135-kDa B-lymphocyte restricted type-I transmembrane sialoglycoprotein of the immunoglobulin (Ig) superfamily, with seven Ig-like domains and three cytoplasmic ITIMs (immunoreceptor tyrosine-based inhibitory motifs) [14]. CD22 appears intracellularly during the late pro-B-cell stage of ontogeny, shifting to the plasma membrane with B-cell maturation. CD22 is expressed at low levels on immature B cells, expressed at higher levels on mature IgM+, IgD+ B cells, and absent on different