Active chronic sarcoidosis is characterized by increased transitional blood B cells, increased IL-10-producing regulatory B cells and high BAFF levels

PLoS One. 2012;7(8):e43588. doi: 10.1371/journal.pone.0043588. Epub 2012 Aug 22.

Abstract

Background: Sarcoidosis 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 findings: We 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/significance: These 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • B-Cell Activating Factor / blood*
  • B-Lymphocytes, Regulatory / cytology*
  • B-Lymphocytes, Regulatory / metabolism*
  • Case-Control Studies
  • Cell Count
  • Chronic Disease
  • Female
  • Granuloma / blood
  • Granuloma / complications
  • Humans
  • Hypergammaglobulinemia / complications
  • Interleukin-10 / biosynthesis*
  • Male
  • Middle Aged
  • Phenotype
  • Sarcoidosis / blood*
  • Sarcoidosis / complications
  • Sarcoidosis / immunology*
  • Time Factors
  • Young Adult

Substances

  • B-Cell Activating Factor
  • TNFSF13B protein, human
  • Interleukin-10

Grants and funding

Bourse du Fonds d’Etudes et de Recherche du Corps Médical de l’AP-HP, Société française de Dermatologie (SFD), Société française de Recherche Dermatologique (SRD), Legs Poix. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.