title: B cell-activating factor of the tumor necrosis factor family (BAFF) is expressed under stimulation by interferon in salivary gland epithelial cells in primary Sjögren's syndrome.
abstract: B cell-activating factor (BAFF) has a key role in promoting B-lymphocyte activation and survival in primary Sjögren's syndrome (pSS). The cellular origin of BAFF overexpression in salivary glands of patients with pSS is not fully known. We investigated whether salivary gland epithelial cells (SGECs), the main targets of autoimmunity in pSS, could produce and express BAFF. We used quantitative RT-PCR, ELISA and immunocytochemistry in cultured SGECs from eight patients with pSS and eight controls on treatment with IL-10, tumor necrosis factor alpha (TNF-alpha), IFN-alpha and IFN-gamma. At baseline, BAFF expression in SGECs was low in pSS patients and in controls. Treatment with IFN-alpha, IFN-gamma and TNF-alpha + IFN-gamma increased the level of BAFF mRNA in pSS patients (the mean increases were 27-fold, 25-fold and 62-fold, respectively) and in controls (mean increases 19.1-fold, 26.7-fold and 17.7-fold, respectively), with no significant difference between patients and controls. However, in comparison with that at baseline, stimulation with IFN-alpha significantly increased the level of BAFF mRNA in SGECs of pSS patients (p = 0.03) but not in controls (p = 0.2), which suggests that SGECs of patients with pSS are particularly susceptible to expressing BAFF under IFN-alpha stimulation. Secretion of BAFF protein, undetectable at baseline, was significantly increased after IFN-alpha and IFN-gamma stimulation both in pSS patients (40.8 +/- 12.5 (+/- SEM) and 47.4 +/- 18.7 pg/ml, respectively) and controls (24.9 +/- 8.0 and 9.0 +/- 3.9 pg/ml, respectively), with no significant difference between pSS and controls. Immunocytochemistry confirmed the induction of cytoplasmic BAFF expression after stimulation with IFN-alpha and IFN-gamma. This study confirms the importance of resident cells of target organs in inducing or perpetuating autoimmunity. Demonstrating the capacity of SGECs to express and secrete BAFF after IFN stimulation adds further information to the pivotal role of these epithelial cells in the pathogenesis of pSS, possibly after stimulation by innate immunity. Our results suggest that an anti-BAFF therapeutic approach could be particularly interesting in pSS.
authors.affiliation: Rhumatologie, Institut Pour la Santé et la Recherche Médicale (INSERM) U 802, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Sud 11, 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Ittah
authors.forename: Corinne
authors.initials: C
authors.lastname: Miceli-Richard
authors.forename: Jacques-
authors.initials: J
authors.lastname: Eric Gottenberg
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lavie
authors.forename: Thierry
authors.initials: T
authors.lastname: Lazure
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ba
authors.forename: Jérémie
authors.initials: J
authors.lastname: Sellam
authors.forename: Christine
authors.initials: C
authors.lastname: Lepajolec
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
mesh_terms: D000328:Adult; D053264:B-Cell Activating Factor; D016022:Case-Control Studies; D002478:Cells, Cultured; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012469:Salivary Glands / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D012859:Sjogren's Syndrome / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D053264:B-Cell Activating Factor; D004338:Drug Combinations; D016898:Interferon-alpha; D008565:Membrane Proteins; D012333:RNA, Messenger; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma