Type I interferon pathway assays in studies of rheumatic and musculoskeletal diseases: a systematic literature review informing EULAR points to consider
Mary K Crow,
Lars Rönnblom,
Dimitrios T Boumpas,
Robert Biesen,
George Bertsias,
Marie-Louise Frémond,
Marie Wahren-Herlenius,
Giulio Cavalli,
PG Conaghan,
Maija-Leena Eloranta,
Javier Rodríguez-Carrio,
Marianne Visser,
Agata Burska,
Willem A Dik,
Ed Vital,
Jan Rehwinkel,
Marjan Versnel
Affiliations
Mary K Crow
Hospital for Special Surgery, Weill Cornell Medical College, Mary Kirkland Center for Lupus Research, New York, USA
Lars Rönnblom
Uppsala University, Department of Medical Sciences, Rheumatology, Uppsala, Sweden
Dimitrios T Boumpas
University of Crete, Medical School, Department of Rheumatology-Clinical Immunology, Heraklion, Greece
Robert Biesen
Charité University Medicine Berlin, Department of Rheumatology, Berlin, Germany
George Bertsias
University of Crete, Medical School, Department of Rheumatology-Clinical Immunology, Heraklion, Greece
Marie-Louise Frémond
Université de Paris Cité, Hôpital Necker-Enfants Malades, Immuno-Hématologie et Rhumatologie pédiatriques, Paris, France
Marie Wahren-Herlenius
Karolinska Institutet, Division of Rheumatology, Stockholm, Sweden
Giulio Cavalli
Unit of Immunology, Rheumatology, Allergy and Rare Diseases, Vita-Salute San Raffaele University, Milan, Italy
PG Conaghan
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds & NIHR Leeds Biomedical Research Centre, Leeds, UK
Maija-Leena Eloranta
Uppsala University, Department of Medical Sciences, Rheumatology, Uppsala, Sweden
Javier Rodríguez-Carrio
University of Oviedo, Area of Immunology, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
Marianne Visser
University of Crete, Medical School, Department of Internal Medicine, Heraklion, Greece
Agata Burska
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds & NIHR Leeds Biomedical Research Centre, Leeds, UK
Willem A Dik
Erasmus MC, University Medical Center Rotterdam, Laboratory Medical Immunology, Department of Immunology, Rotterdam, Netherlands Immunology, Rotterdam, The Netherlands
Ed Vital
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds & NIHR Leeds Biomedical Research Centre, Leeds, UK
Jan Rehwinkel
Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, UK
Marjan Versnel
Erasmus MC, Department of Immunology, Rotterdam, The Netherlands
Objectives To systematically review the literature for assay methods that aim to evaluate type I interferon (IFN-I) pathway activation and to harmonise-related terminology.Methods Three databases were searched for reports of IFN-I and rheumatic musculoskeletal diseases. Information about the performance metrics of assays measuring IFN-I and measures of truth were extracted and summarised. A EULAR task force panel assessed feasibility and developed consensus terminology.Results Of 10 037 abstracts, 276 fulfilled eligibility criteria for data extraction. Some reported more than one technique to measure IFN-I pathway activation. Hence, 276 papers generated data on 412 methods. 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). Principles of each assay are summarised for content validity. Concurrent validity (correlation with other IFN assays) was presented for n=150/412 assays. Reliability data were variable and provided for 13 assays. Gene expression and immunoassays were considered most feasible. Consensus terminology to define different aspects of IFN-I research and practice was produced.Conclusions Diverse methods have been reported as IFN-I assays and these differ in what elements or aspects of IFN-I pathway activation they measure and how. No ‘gold standard’ represents the entirety of the IFN pathway, some may not be specific for IFN-I. Data on reliability or comparing assays were limited, and feasibility is a challenge for many assays. Consensus terminology should improve consistency of reporting.
