Association between type I interferon pathway activation and clinical outcomes in 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,
Maija-Leena Eloranta,
Javier Rodríguez-Carrio,
Marianne Visser,
P G Conaghan,
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
Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden
Dimitrios T Boumpas
Department of Internal Medicine, University of Crete, Medical School, Heraklion, Greece
Robert Biesen
Department of Rheumatology, Charité University Medicine Berlin, Berlin, Germany
George Bertsias
Department of Rheumatology-Clinical Immunology, University of Crete, Medical School, 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
Maija-Leena Eloranta
Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden
Javier Rodríguez-Carrio
Area of Immunology, University of Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Asturias, Spain
Marianne Visser
EULAR, PARE Patient Research Partners, Amsterdam, The Netherlands
P G Conaghan
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds & NIHR Leeds Biomedical Research Centre, Leeds, UK
Agata Burska
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds & NIHR Leeds Biomedical Research Centre, Leeds, UK
Willem A Dik
Laboratory Medical Immunology, department of Immunology, Erasmus MC University Medical Center 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
Department of Immunology, Erasmus MC University Medical Center Rotterdam, The Netherlands
Background Type I interferons (IFN-I) contribute to a broad range of rheumatic and musculoskeletal diseases (RMDs). Compelling evidence suggests that the measurement of IFN-I pathway activation may have clinical value. Although several IFN-I pathway assays have been proposed, the exact clinical applications are unclear. We summarise the evidence on the potential clinical utility of assays measuring IFN-I pathway activation.Methods A systematic literature review was conducted across three databases to evaluate the use of IFN-I assays in diagnosis and monitor disease activity, prognosis, response to treatment and responsiveness to change in several RMDs.Results Of 366 screened, 276 studies were selected that reported the use of assays reflecting IFN-I pathway activation for disease diagnosis (n=188), assessment of disease activity (n=122), prognosis (n=20), response to treatment (n=23) and assay responsiveness (n=59). Immunoassays, quantitative PCR (qPCR) and microarrays were reported most frequently, while systemic lupus erythematosus (SLE), rheumatoid arthritis, myositis, systemic sclerosis and primary Sjögren’s syndrome were the most studied RMDs. The literature demonstrated significant heterogeneity in techniques, analytical conditions, risk of bias and application in diseases. Inadequate study designs and technical heterogeneity were the main limitations. IFN-I pathway activation was associated with disease activity and flare occurrence in SLE, but their incremental value was uncertain. IFN-I pathway activation may predict response to IFN-I targeting therapies and may predict response to different treatments.Conclusions Evidence indicates potential clinical value of assays measuring IFN-I pathway activation in several RMDs, but assay harmonisation and clinical validation are urged. This review informs the EULAR points to consider for the measurement and reporting of IFN-I pathway assays.
