Elsevier

Journal of Autoimmunity

Volume 39, Issue 3, September 2012, Pages 161-167
Journal of Autoimmunity

Review
B cells in Sjögren's syndrome: From pathophysiology to diagnosis and treatment

https://doi.org/10.1016/j.jaut.2012.05.014Get rights and content

Abstract

Primary Sjögren's syndrome (pSS) is a chronic autoimmune systemic disease, characterized by a lymphoplasmocytic infiltration and a progressive destruction of salivary and lachrymal glands, leading to ocular and mouth dryness. T cells were originally considered to play the initiating role in the autoimmune process, while B cells were restricted to autoantibody production. However, recent years have seen growing evidence that the roles of B cells in pSS pathophysiology are multiple, and that these cells may actually play a central role in the development of the disease. B cells are over-stimulated and produce excessive amounts of immunoglobulins and various autoantibodies. Peripheral blood and salivary-gland B-cell subset distribution is altered, leading to the constitution of ectopic germinal centers where auto-reactive clones may escape tolerance checkpoints. B cells control T-cell activation by different means: B effector cells guide Th1 or Th2 differentiation, whereas regulatory B cells inhibit T-cell proliferation. Several B-cell specific cytokines, such as BAFF or Flt-3L, are instrumental in the occurrence of B-cell dysfunction. Chronic and excessive stimulation of B cells may lead to the development of lymphoma in pSS patients. Autoantibodies and blood B-cell subset analysis are major contributors of a clinical diagnosis of pSS. These considerations led to the development of B-cell depletion therapies for the management of pSS. Rituximab, a monoclonal antibody to CD20, is the best studied biologics in pSS, but other treatments hold promise, targeting for example CD22 or BAFF. Thus, during the last 20 years, the understanding of the multifaceted roles of B cells in pSS has revolutionized the management of this complex disease.

Highlights

► Recent data demonstrated the central roles of B cells in the pathogenesis of pSS. ► Peripheral blood and salivary-gland B-cell subset distribution is altered during pSS. ► The cytokine BAFF is instrumental in the occurrence of B-cell dysfunction. ► Autoantibodies and blood B-cell subset analysis are important for the diagnosis. ► B-cell directed therapies hold promise in the treatment of the disease.

Introduction

Primary Sjögren's syndrome (pSS) is a chronic autoimmune systemic disease, characterized by a lymphoplasmocytic infiltration and a progressive destruction of salivary and lachrymal glands, leading to ocular and mouth dryness. Beyond these sicca symptoms, half of the patients develop extraglandular features, including arthritis, lung interstitial disease, nervous system involvement, or tubular nephropathy.

T cells were originally considered to play the initiating role in the autoimmune process, while B cells were restricted to autoantibody production. However, recent years have seen growing evidence that the roles of B cells in pSS pathophysiology are multiple, and that these cells may actually play a central role in the development of the disease. These considerations led to the development of B-cell depletion therapies for the management of pSS.

Pierre Youinou was the founder and leader of Brest University Laboratory of Immunology, and retired in 2011. He devoted his working life to the study of B cells, and especially of their implication in autoimmune diseases. We will present in this paper some of his contributions to the understanding of the roles of B cells in pSS.

Section snippets

Immunoglobulins and autoantibodies during Sjögren's syndrome

B-cell hyperactivity is a hallmark of pSS. Activation of B cells results in hypergammaglobulinemia and in the production of various autoantibodies. Elevated IgA level is a common finding during pSS, and these immunoglobulins can display rheumatoid factor (RF) activity [1]. As a consequence, circulating IgA-containing immune complexes can be detected in a high proportion of patient with pSS, and are strongly associated with abnormal salivary-gland biopsy [2]. The glycosylation of serum

Anti-SSA/SSB and other autoantibodies

Anti-SSA and anti-SSB antibodies are highly associated with a clinical diagnosis of pSS. Two types of anti-Ro/SSA antibodies have been described, anti-SSA-52 kDa (aSSA52) and anti-SSA-60 kDa (aSSA60), each specific to different antigens. Anti-Ro/SSA52 autoantibodies are more frequent than other autoantibodies possibly because of the antigen's accessible and ubiquitous nature [51]. The presence of anti-SSA or anti-SSB is a major item of AECG criteria [9]. However, 20–40% of the patients

Conclusions

B lymphocytes are major contributors to the pathogenesis of SS. With the advent of biologic response modifiers, these data may be used in the development of novel approaches to therapy. Thus, B-cell depletion and modulation of the BAFF/APRIL system may hold significant promise for the treatment for patients with pSS. Our group in Brest is particularly honored to recognize Pierre Youinou and this special issue. Pierre is not only a dedicated scholar, but has also been a good friend and mentor of

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