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- Burska, A, et al.
(författare)
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TYPE I INTERFERON PATHWAY ASSAYS IN PATIENTS WITH RHEUMATIC AND MUSCULOSKELETAL DISEASES - SYSTEMATIC LITERATURE REVIEW (SLR) AND DEVELOPMENT OF CONSENSUS TERMINOLOGY FROM A EULAR TASKFORCE
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 415-415
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The interferon (IFN) pathway is a complex system with multiple proteins and diverse downstream effects on gene and protein expression. IFNs have been implicated in multiple RMDs. Despite significant potential, IFN assays have not progressed into clinical practice.Objectives:To perform a SLR on IFN assays in RMDs and propose a consensus terminology.Methods:OvidMedline, Embase and Web of Science were searched for reports of IFN and RMDs up to October 2019. Information about the properties of assays measuring type I IFN and measures of truth were extracted and summarised. Terminology was agreed through an interactive consensus process with reference to the existing evidence.Results:10037 abstracts were identified. 275 fulfilled eligibility criteria, and were used for data extraction. Some used more than one technique to measure IFN-I pathway activation. Hence, 275 papers generated data on 393 methods. There was great heterogeneity in the methods used and presentation of results. IFN-I pathway activation was measured using: qPCR (n=121), immunoassays (n=101), microarray (n=69), reporter cell assay (n=38), DNA methylation (n=14), flow cytometry (n=14), cytopathic effect assay (n=11), RNA sequencing (n=9), Plaque reduction assay (n=8), Nanostring (n=5), bisulphite sequencing (n=3). All papers fulfilled Face Validity. Due to lack of gold standard for IFN-I pathway activation, evidence of criterion validity was variable. Concurrent validity was presented for n=150 assays. The terminology used to describe aspects of type I IFN pathway activation was not consistent, so a consensus terminology for IFN research (Table 1) was proposed by the taskforce.Table 1.Consensus terminologyTermAbbreviationDefinitionInterferonIFNProteins with anti-viral activity; IFNs are mediators of an anti-viral response. They belong to the Type I, Type II and Type III IFN families.Type I interferonIFN-IThe IFNs alpha, beta, omega, kappa, epsilon, secreted by any nucleated cell, and binding to the IFNAR, which is expressed on any nucleated cell.Type II interferonIFN-IIIFN gamma, mostly secreted by T cells, binding to the IFNGR, which is expressed on most leucocytes.Type III interferonIFN-IIIIFN lambda, which are structurally more similar to IL-10 but share downstream signalling and gene expression with IFN-I.Interferon-stimulated genesISGsGenes whose expression is known to be upregulated by any kind of IFN. Individual ISGs may not exclusively represent Type I IFN pathway activation.Type I Interferon pathway activationAny evidence for function of the components of the Type I IFN pathway. This includes: secretion of a Type I IFN protein, binding to the IFNAR, initiation of JAK/STAT signalling pathways, expression of IFN-stimulated genes, expression of IFN-stimulated proteins.Type I interferon pathway assayAn assay measuring one or more components of the Type I IFN pathway at a molecular or functional level.Interferon stimulated gene expression signatureA qualitative description of coordinated expression of a set of ISGs that is indicative of Type I IFN pathway activation.Interferon stimulated gene expression scoreA quantitative variable derived from expression of a defined set of ISGs that is indicative of Type I IFN pathway activation.Interferon stimulated protein scoreA variable derived from expression of a defined set of soluble biomarkers known to be upregulated by IFN, although not specific for Type I IFN.InterferonopathyMonogenic diseases in which there is constitutive Type I IFN pathway activation with a causal role in pathology. The clinical picture may resemble rheumatic musculoskeletal diseases. However, most diseases with IFN pathway activation are not Interferonopathies.Conclusion:Diverse methods have been reported as IFN assays and these differ in what elements of type IFN-I pathway activation they measure. The taskforce consensus terminology on type I IFN reporting should be considered for research and clinical applications.Disclosure of Interests:Agata Burska: None declared, Javier Rodriguez Carrio: None declared, Philip G Conaghan: None declared, Willem A Dik: None declared, Robert Biesen: None declared, Maija-leena Eloranta: None declared, Giulio Cavalli: None declared, Marianne Visser: None declared, Dimitrios Boumpas: None declared, George Bertsias: None declared, Marie Wahren-Herlenius: None declared, Jan Rehwinkel: None declared, Marie-Louise Frémond: None declared, Mary K. Crow Consultant of: AstraZeneca, Bristol Meyers Squibb, Lilly, Shannon Pharmaceuticals, Grant/research support from: Gilead, Lars Ronnblom Consultant of: AstraZeneca, Edward Vital Speakers bureau: GSK, Consultant of: AURINIA, SANDOZ, GSK, AstraZeneca, Roche, Modus, Grant/research support from: AstraZeneca, Marjan Versnel: None declared
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- Olsson, Peter, et al.
(författare)
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Associations of cigarette smoking with disease phenotype and type I interferon expression in primary Sjogren's syndrome
- 2019
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Ingår i: Rheumatology International. - : Springer Science and Business Media LLC. - 0172-8172 .- 1437-160X. ; 39:9, s. 1575-1584
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have shown a negative association between smoking and primary Sjogren'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 Sjogren's Syndrome Patient Reported Index (ESSPRI) form and a structured questionnaire regarding smoking habits. EULAR Sjogren'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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- Rodriguez-Carrio, Javier, et al.
(författare)
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2022 EULAR points to consider for the measurement, reporting and application of IFN-I pathway activation assays in clinical research and practice
- 2023
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 82:6, s. 754-762
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Tidskriftsartikel (refereegranskat)abstract
- Background: Type I interferons (IFN-Is) play a role in a broad range of rheumatic and musculoskeletal diseases (RMDs), and compelling evidence suggests that their measurement could have clinical value, although testing has not progressed into clinical settings.Objective: To develop evidence-based points to consider (PtC) for the measurement and reporting of IFN-I assays in clinical research and to determine their potential clinical utility.Methods: EULAR standardised operating procedures were followed. A task force including rheumatologists, immunologists, translational scientists and a patient partner was formed. Two systematic reviews were conducted to address methodological and clinical questions. PtC were formulated based on the retrieved evidence and expert opinion. Level of evidence and agreement was determined.Results: Two overarching principles and 11 PtC were defined. The first set (PtC 1-4) concerned terminology, assay characteristics and reporting practices to enable more consistent reporting and facilitate translation and collaborations. The second set (PtC 5-11) addressed clinical applications for diagnosis and outcome assessments, including disease activity, prognosis and prediction of treatment response. The mean level of agreement was generally high, mainly in the first PtC set and for clinical applications in systemic lupus erythematosus. Harmonisation of assay methodology and clinical validation were key points for the research agenda.Conclusions: IFN-I assays have a high potential for implementation in the clinical management of RMDs. Uptake of these PtC will facilitate the progress of IFN-I assays into clinical practice and may be also of interest beyond rheumatology.
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