title: Elevated serum BAFF levels in patients with sarcoidosis: association with disease activity.
abstract: OBJECTIVE
  The purpose of this study was to determine serum levels of B-cell-activating factor (BAFF) and its clinical association in patients with sarcoidosis. METHODS; Serum levels of BAFF from 37 patients and 21 healthy subjects were examined by ELISA. Serum angiotensin-converting enzyme (ACE), lysozyme and IFN-γ levels in sarcoidosis patients were also measured. Isolated monocytes cultured with IFN-γ, IL-4 or IL-10 and their expression of membrane and soluble BAFF were analysed by flow cytometry or ELISA. Peripheral B cell subsets were analysed by flow cytometry. BAFF expression in the granuloma of the skin was examined by immunohistochemistry. ANAs were determined by indirect IF using HEp-2 cells as a substrate.
  
  
  RESULTS
  Serum BAFF levels were significantly elevated in sarcoidosis patients when compared with healthy controls. The frequency of skin and eye involvement was significantly higher in patients with elevated serum BAFF than in patients with normal levels. Serum BAFF levels were correlated with serum levels of ACE, lysozyme and IFN-γ. Immunostaining of anti-BAFF in the skin revealed BAFF expression by epithelioid cells of granuloma. In vitro, IFN-γ induced membrane-bound BAFF expression on monocytes and secretion of soluble BAFF by isolated monocytes. In the peripheral blood, sarcoidosis patients showed increased naïve B cells with a reciprocal decrease in memory B cells and plasmablasts. Seventeen of 26 (65%) sarcoidosis patients exhibited ANA positivity.
  
  
  CONCLUSIONS
  Serum BAFF levels can be used as a surrogate marker of disease activity in sarcoidosis patients. Increased BAFF may be related to the pathogenesis of sarcoidosis.
authors.affiliation: Department of Dermatology, Kansai Medical University, Hirakata, Osaka, Japan. uedaik@hirakata.kmu.ac.jp
authors.forename: Ikuko
authors.initials: I
authors.lastname: Ueda-Hayakawa
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Tanimura
authors.forename: Manabu
authors.initials: M
authors.lastname: Osawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwasaka
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ohe
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Yamazaki
authors.forename: Kana
authors.initials: K
authors.lastname: Mizuno
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okamoto
mesh_terms: D000368:Aged; D053264:B-Cell Activating Factor / Q000097:blood*; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009113:Muramidase / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D012507:Sarcoidosis / Q000097:blood*; D012720:Severity of Illness Index
chemical_list: D053264:B-Cell Activating Factor; D015415:Biomarkers; C505719:TNFSF13B protein, human; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D009113:Muramidase; D007703:Peptidyl-Dipeptidase A
keywords: B cell; B-cell-activating factor (BAFF); monocyte; sarcoidosis