Prevalence of interferon type I signature in CD14 monocytes of patients with Sjogren'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.
Department of Immunology, Erasmus MC, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. z.brkic@erasmusmc.nl
Zana
Z
Brkic
Naomi I
NI
Maria
Cornelia G
CG
van Helden-Meeuwsen
Joop P
JP
van de Merwe
Paul L
PL
van Daele
Virgil A
VA
Dalm
Manon E
ME
Wildenberg
Wouter
W
Beumer
Hemmo A
HA
Drexhage
Marjan A
MA
Versnel
D000328:Adult; D000368:Aged; D053264:B-Cell Activating Factor / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D015995:Prevalence; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012859:Sjogren's Syndrome / Q000453:epidemiology* / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D053264:B-Cell Activating Factor; D015415:Biomarkers; D007370:Interferon Type I; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; C505719:TNFSF13B protein, human