Active Chronic Sarcoidosis is Characterized by Increased Transitional Blood B Cells, Increased IL-10-Producing Regulatory B Cells and High BAFF Levels

Anne Saussine,Abdellatif Tazi,Michel Rybojad,Séverine Feuillet,Caroline Juillard,Martine Bagot,Armand Bensussan,Anne Janin,Jean-David Bouaziz,Valérie Dessirier,Anne Bergeron,Fatiha Bouhidel,Yoshihiko Hoshino

doi:10.1371/journal.pone.0043588

Anne Saussine, Abdellatif Tazi + Show 11 more

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https://doi.org/10.1371/journal.pone.0043588

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Abstract

BackgroundSarcoidosis is a multisystemic disease of unknown etiology characterized by a disproportionate Th1 granulomatous immune response in the organs involved. Plasmatic hypergammaglobulinemia and B cell accumulation in granulomatous lesions suggest the possible role of humoral immune responses in the pathogenesis of sarcoidosis. The purpose of this study is to describe B cell peripheral compartment in sarcoidosis.Methodology/Principal FindingsWe analyzed blood B cell subsets and BAFF levels in 33 patients with chronic sarcoidosis (active sarcoidosis n = 18; inactive sarcoidosis n = 15) and 18 healthy donors. Active chronic sarcoidosis patients had significantly less circulating memory B cells (p<0.01), more transitional (p<0.01) and increased numbers of IL-10-producing regulatory B cells (p<0.05) compared with healthy donors and patients with inactive sarcoidosis. BAFF serum levels were significantly higher in patients with active sarcoidosis (p<0.01 versus healthy donors and inactive sarcoidosis patients) and strongly correlated with serum hypergammaglobulinemia (r = 0.53, p<0.01) and angiotensin converting enzyme levels (r = 0.61, p = <0.01).Conclusions/SignificanceThese data show that there is an altered B cell homeostasis in active sarcoidosis and suggest BAFF antagonist drugs as potential new treatments of this disease.

Highlights

Sarcoidosis is a multisystemic disease of unknown etiology [1] characterized by a disproportionate Th1 granulomatous immune response in the organs involved [2,3,4,5,6]
Active sarcoidosis has been associated with plasmatic hypergammaglobulinemia [5], B cell accumulation has been shown in pulmonary lesions [6] and a beneficial effect of anti-CD20 monoclonal antibody B cell-depleting therapy has been reported in select patients [7,8,9]
Increased transitional B cells, increased IL-10-producing regulatory B cells and increased B cellactivating factor from the TNF family (BAFF) levels could be responsible for the physiopathology of the disease because these abnormalities were not found in patients with inactive sarcoidosis

Summary

Introduction

Sarcoidosis is a multisystemic disease of unknown etiology [1] characterized by a disproportionate Th1 granulomatous immune response in the organs involved [2,3,4,5,6]. Innate and T cell immunity play key roles in the pathogenesis of sarcoidosis [1,2,3,4], several arguments suggest a potential involvement of humoral immune responses in this disease. B cells are generally considered positive regulators of the immune response in inflammatory diseases [10], but recent studies have described a new subset of B cells secreting interleukin-10 (IL-10) that down-regulate immune responses: regulatory B cells (Bregs) in mice and humans [11,12,13,14,15,16,17,18,19]. Plasmatic hypergammaglobulinemia and B cell accumulation in granulomatous lesions suggest the possible role of humoral immune responses in the pathogenesis of sarcoidosis. The purpose of this study is to describe B cell peripheral compartment in sarcoidosis

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