Systemic interferon type I and type II signatures in primary Sjögren’s syndrome reveal differences in biological disease activity

Bodewes, Iris L A; Al-Ali, Shereen; Helden-Meeuwsen, Cornelia G van; Maria, Naomi I.; Tarn, Jessica; Lendrem, Dennis; Schreurs, Marco W. J.; Steenwijk, Eline C.; Daele, Paul L A van; Both, Tim; Bowman, Simon; Griffiths, Bridget; Ng, Wan‐Fai; Registry, . Uk Primary Sjögren's Syndrome; Versnel, Marjan A.

doi:10.1093/rheumatology/kex490

Cited by 94 publications

(112 citation statements)

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“…The presence of an elevated expression of these genes is called an "IFN-signature". Systemic type I IFN signature is found in a large fraction of pSS patients [5]. The type I IFN signature has also been shown to be associated with presence of anti-SSA and anti-SSB antibodies, and hypergammaglobulinemia [5].…”

Section: Introductionmentioning

confidence: 99%

“…Systemic type I IFN signature is found in a large fraction of pSS patients [5]. The type I IFN signature has also been shown to be associated with presence of anti-SSA and anti-SSB antibodies, and hypergammaglobulinemia [5]. Disease activity as evaluated by the European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI) has been associated to type I IFN signature previously [6,7] although some studies fail to confirm the association [5].…”

Section: Introductionmentioning

confidence: 99%

“…The type I IFN signature has also been shown to be associated with presence of anti-SSA and anti-SSB antibodies, and hypergammaglobulinemia [5]. Disease activity as evaluated by the European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI) has been associated to type I IFN signature previously [6,7] although some studies fail to confirm the association [5]. On the contrary, the presence of the IFN signature has been associated with lower patient-reported symptoms as evaluated by the EULAR Sjögren's syndrome patient-reported index (ESS-PRI) [5].…”

Section: Introductionmentioning

confidence: 99%

“…Disease activity as evaluated by the European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI) has been associated to type I IFN signature previously [6,7] although some studies fail to confirm the association [5]. On the contrary, the presence of the IFN signature has been associated with lower patient-reported symptoms as evaluated by the EULAR Sjögren's syndrome patient-reported index (ESS-PRI) [5]. We recently published an epidemiological study showing that smoking was associated with a lower risk of later being diagnosed with pSS [8].…”

Section: Introductionmentioning

confidence: 99%

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Associations of cigarette smoking with disease phenotype and type I interferon expression in primary Sjögren’s syndrome

Olsson

Bodewes²,

Nilsson

et al. 2019

Rheumatol Int

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Several studies have shown a negative association between smoking and primary Sjögren's syndrome (pSS), and smoking may interfere with the immune response. The purpose of this study was to investigate if smoking affects disease activity and disease phenotype in pSS. In this cross-sectional study, consecutive pSS patients filled out the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) form and a structured questionnaire regarding smoking habits. EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) scores were calculated and blood samples were analysed for type I interferon signature using RT-PCR. Of 90 patients (93% women, median age 66.5 years), 72% were type I IFN signature positive and 6, 42 and 53% were current, former and never smokers, respectively. No significant differences by smoking status were found regarding ESSDAI total score, activity in the ESSDAI domains or type I IFN signature. Patients with a higher cumulative cigarette consumption (≥ median) had higher scores in ESSPRI total [5.0 (3.0-6.3) vs 8.0 (6.0-8.3); p < 0.01] and ESSPRI sicca and pain domains. Comparing type I IFN signature negative and positive patients, the latter had significantly lower activity in ESSDAI articular domain (7/25 vs 3/64; p < 0.01) and lower scores in ESSPRI total [7.7 (5.2-8.2) vs 6.0 (4.0-7.7); p = 0.04].Smoking was not associated with disease phenotype although patients with a higher cumulative cigarette consumption had worse symptoms in some disease domains. Current smokers were few making it difficult to draw any firm conclusions about associations to current smoking.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Associations of cigarette smoking with disease phenotype and type I interferon expression in primary Sjögren’s syndrome

Olsson

Bodewes²,

Nilsson

et al. 2019

Rheumatol Int

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“…Although profiling of the blood transcriptome revealed a prevalent IFN type I signature in SLE, blocking the IFN pathway only showed efficacy in a subset of adult-onset SLE patients. Recent studies revealed that other gene signatures like IFN type I+II (M5.12), B cell, plasmablast and neutrophil signatures are important in SLE as well and some could be linked to specific clinical phenotypes [2,3]. Assessment of these novel gene signatures in SLE may help to distinguish specific disease phenotypes and guide treatment choices in the future.…”

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confidence: 99%

Thu0240 gene Expression Signatures Are Related to Specific Subsets of Patients With Systemic Lupus Erythematosus

Wahadat

Groot

Helden-Meeuwsen

et al. 2019

Poster Presentations

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Background:Systemic lupus erythematosus (SLE) is a heterogeneous, lifelong autoimmune disease, with a more severe phenotype in children compared to adult-onset SLE [1]. To date, approved drugs are by far not effective enough and have significant side effects, especially due to the use of prednisone. Although profiling of the blood transcriptome revealed a prevalent IFN type I signature in SLE, blocking the IFN pathway only showed efficacy in a subset of adult-onset SLE patients. Recent studies revealed that other gene signatures like IFN type I+II (M5.12), B cell, plasmablast and neutrophil signatures are important in SLE as well and some could be linked to specific clinical phenotypes [2, 3]. Assessment of these novel gene signatures in SLE may help to distinguish specific disease phenotypes and guide treatment choices in the future.Objectives:To determine and compare the expression of the IFN-, B cell-, plasmablast- and neutrophil signatures in pediatric and adult SLE patients.Methods:The IFN-I-, M5.12-, neutrophil-, B cell- and plasmablast signatures were measured using real-time quantitative PCR expression on whole blood RNA samples. To identify correlated groups of genes and reduce data complexity, the expression of a selection of genes identified by blood transcriptional profiling was tested and subsequently added to a principle component analysis to obtain a limited set of genes (2-5 per signatures), that reliably represent a specific signature.These signatures were analyzed in three separate pilot cohorts of healthy controls (n=12), pediatric- (n=22; average disease duration=0.9 years) and adult SLE patients (n=36; average disease duration=17.4 years).Results:IFN-I signature was significantly higher in SLE patients compared to healthy controls (p=0.001). M5.12 (p=0.05) and the B cell (p=0.0001) signature showed a significant difference between the pediatric and adult cohort while there was no difference between the neutrophil- and plasmablast signatures in the two patient groups. Interestingly, the B cell gene signature, correlated with age (p=0.0001, r= -0.49) and disease duration (p=0.001, r= -0.42). In addition, the possible correlation between the IFN-I signature and the other signatures was investigated. While the IFN-I signature in both adults and children showed a significant positive correlation to the M5.12- (p<0.0001, r=0.97; p=0.006, r=0.61) and plasmablast (p=0.03, r=0.37; p=0.0037, r=0.62) signature expression, only adult patients had a significant positive correlation of the IFN-I signature to the neutrophil signature (p=0.001, r=0.55).Conclusion:In this pilot study we found significant differences in gene expression signatures between pediatric and adult SLE patients. Additionally, age and disease duration were significantly correlated to the B cell gene signature. These findings indicate differences in transcriptional profiles in specific subsets of SLE patients which could have therapeutic consequences.References:[1] Groot, N., et al., Long-term clinical outcomes in a cohort of adults with...

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Sjögren's Syndrome as a Proof of Concept of the Hyperstimulation Syndrome

Borba,

Shoenfeld

2024

Autoimmune Disorders

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Systemic interferon type I and type II signatures in primary Sjögren’s syndrome reveal differences in biological disease activity

Abstract: Systemic IFN activation is associated with higher activity only in the ESSDAI biological domain but not in other domains or the total score. Our data raise the possibility that the ESSDAI biological domain score may be a more sensitive endpoint for trials targeting either IFN pathway.

Cited by 94 publications

References 44 publications

Associations of cigarette smoking with disease phenotype and type I interferon expression in primary Sjögren’s syndrome

Associations of cigarette smoking with disease phenotype and type I interferon expression in primary Sjögren’s syndrome

Thu0240 gene Expression Signatures Are Related to Specific Subsets of Patients With Systemic Lupus Erythematosus

Sjögren's Syndrome as a Proof of Concept of the Hyperstimulation Syndrome

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