Prevalence of interferon type I signature in CD14 monocytes of patients with Sjögren's syndrome and association with disease activity and BAFF gene expression

• Published in: Annals of the rheumatic diseases Vol. 72; no. 5; pp. 728 - 735
• Main Authors: Brkic, Zana, Maria, Naomi I, van Helden-Meeuwsen, Cornelia G, van de Merwe, Joop P, van Daele, Paul L, Dalm, Virgil A, Wildenberg, Manon E, Beumer, Wouter, Drexhage, Hemmo A, Versnel, Marjan A
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and European League Against Rheumatism 01.05.2013; Elsevier Limited; BMJ Group
• Series: Extended report
• Subjects: Adult; Aged; Autoimmune diseases; B-Cell Activating Factor - genetics; Biomarkers - metabolism; Clinical and Epidemiological Research; Dendritic cells; Disease; Female; Gene expression; Gene Expression - immunology; Hepatitis; Histopathology; Humans; Interferon Type I - metabolism; Lipopolysaccharide Receptors - metabolism; Male; Middle Aged; Monocytes - immunology; Monocytes - metabolism; Pathogenesis; Prevalence; Real-Time Polymerase Chain Reaction; RNA, Messenger - metabolism; Sjogren's Syndrome - epidemiology; Sjogren's Syndrome - immunology; Studies; Up-Regulation - immunology
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/annrheumdis-2012-201381

Objective To determine the prevalence of upregulation of interferon (IFN) type I inducible genes, the so called ‘IFN type I signature’, in CD14 monocytes in 69 patients with primary Sjögren's syndrome (pSS) and 44 healthy controls (HC) and correlate it with disease manifestations and expression of B cell activating factor (BAFF). Methods Expression of IFI44L, IFI44, IFIT3, LY6E and MX1 was measured using real time quantitative PCR in monocytes. Expression values were used to calculate IFN type I scores for each subject. pSS patients positive for the IFN type I signature (IFN score≥10) and patients negative for the signature (IFN score<10) were then compared for clinical disease manifestations and BAFF expression. A bioassay using a monocytic cell line was performed to study whether BAFF mRNA expression was inducible by IFN type I activity in serum of patients with pSS. Results An IFN type I signature was present in 55% of patients with pSS compared with 4.5% of HC. Patients with the IFN type I signature showed: (a) higher EULAR Sjögren's Syndrome Disease Activity Index scores; higher anti-Ro52, anti-Ro60 and anti-La autoantibodies; higher rheumatoid factor; higher serum IgG; lower C3, lower absolute lymphocyte and neutrophil counts; (b)higher BAFF gene expression in monocytes. In addition, serum of signature-positive patients induced BAFF gene expression in monocytes. Conclusions The monocyte IFN type I signature identifies a subgroup of patients with pSS with a higher clinical disease activity together with higher BAFF mRNA expression. Such patients might benefit from treatment blocking IFN type I production or activity.