B cell-targeted therapies in Sjögren's syndrome Gabriel J. Tobón, Jacques Olivier Pers, Pierre Youinou, Alain Saraux ⁎ EA2216, IFR148, Université de Bretagne Occidentale, Brest, France Service de Rhumatologie, Centre Hospitalier Universitaire de Brest, Brest, France abstract article info Article history: Received 7 July 2009 Accepted 3 August 2009 Available online 9 August 2009 Keywords: Sjögren's syndrome B cell Rituximab Epratuzumab BAFF Sjögren's syndrome (SS) or autoimmune epithelitis is characterized by focal lymphocytic infiltrates surrounding the tubular epithelium of exocrine glands and by overactivity of the B-cell population. Although T cells were long considered the main effectors in SS, recent findings indicating a key role for B cells have prompted studies of treatments designed to deplete the B-cell population. Among molecules that can be targeted to achieve B-cell depletion, CD20 and CD22 are surface antigens expressed specifically by B lymphocytes; and the cytokine B-cell-activating factor belonging to the TNF family (BAFF) is a TNF receptor ligand involved in B-cell differentiation, survival, and activation. The aim of this review is to discuss the clinical outcomes of SS patients treated with B-cell depletion. © 2009 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224 2. B cells and primary Sjögren's syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224 3. Molecular targets for achieving B-cell depletion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225 4. Anti-CD20 treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225 5. Anti-CD22 treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226 6. Treatments targeting BAFF and APRIL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226 7. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227 Take-home messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Introduction Sjögren's syndrome (SS) is a condition of autoimmune epithelitis that primarily affects females during the fourth and fifth decades of life [1]. The exocrine glands (mainly the salivary and lachrymal glands) exhibit structural lesions characterized by focal lymphocytic infiltrates surrounding the tubular epithelium, and B-cell activity is excessive, resulting in autoantibody production [2]. SS is considered secondary when there is a concomitant systemic autoimmune disease and primary otherwise. The spectrum of SS extends from an organ- specific autoimmune disorder (autoimmune exocrinopathy) to a systemic process that may involve the musculoskeletal system, leading to arthralgia and arthritis [3]. Fatigue is also present and is a major cause of disability. Patients may experience involvement of internal organs such as the lungs, kidneys, nervous system, and gastrointestinal tract. B-cell overactivity in SS manifests as hyper- gammaglobulinemia; production of anti-SSA and anti-SSB autoanti- bodies and of rheumatoid factor (RF); and an increased risk of non- Hodgkin's B-cell lymphoma (NHL) [4,5]. The current treatment consists chiefly in supportive and symptomatic measures aimed at relieving the sicca symptoms. Available drugs improve the dryness, albeit often transiently, but fail to affect the course of the disease. There is a pressing need for disease-modifying drugs to treat patients who have severe organ involvement and factors indicating a high lymphoma risk. Treatments that cause B-cell depletion hold promise as disease-modifying drugs for SS. This review discusses the available clinical data on B-cell depletion used to treat SS. 2. B cells and primary Sjögren's syndrome Although the pathogenesis of SS remains unclear, the classic concept ascribes a key role to the T cell. However, recent evidence Autoimmunity Reviews 9 (2010) 224–228 ⁎ Corresponding author. Rheumatology Unit, Brest University Medical School, BP 824, F29609 Brest, France. Tel.: +33 298 347 267; fax: +33 298 493 627. E-mail address: alain.saraux@chu-brest.fr (A. Saraux). Take-home messages 227 1568-9972/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.autrev.2009.08.001 Contents lists available at ScienceDirect Autoimmunity Reviews journal homepage: www.elsevier.com/locate/autrev