Prevalence of interferon type I signature in CD14 monocytes of patients with Sjögren's syndrome and association with disease activity and BAFF gene expression
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.
|Annals of the Rheumatic Diseases: an international peer-reviewed journal for health professionals and researchers in the rheumatic diseases|
|Organisation||Department of Immunology|
Brkic, Z, Maria, N.I, van Helden-Meeuwsen, C.G, van de Merwe, J.P, van Daele, P.L.A, Dalm, V.A.S.H, … Versnel, M.A. (2013). Prevalence of interferon type I signature in CD14 monocytes of patients with Sjögren's syndrome and association with disease activity and BAFF gene expression. Annals of the Rheumatic Diseases: an international peer-reviewed journal for health professionals and researchers in the rheumatic diseases, 72(5), 728–735. doi:10.1136/annrheumdis-2012-201381