Table 1

Overarching principles and points to consider for the measurement and reporting of IFN-I pathway assays in clinical research and practice

Level of evidenceLevel of agreement (mean±SD), n (%) scorings ≥8/10
Overarching principles
 A.The IFN pathway is a complex system with multiple subtypes of IFNs and diverse downstream effects on gene and protein expression.N/A9.76±0.66
17 (100)
 B. IFN-I pathway activation is a common hallmark in many RMDs. Although IFN-I pathway activation is associated with some clinical manifestations, the utility of IFN-I pathway assays in clinical practice requires further validation for most contexts.N/A9.29±0.98
16 (94.1)
Points to consider
 1. Task force consensus terminology should be considered for reporting IFN assays measurement.59.58±0.79
17 (100)
 2. Existing assays measure different aspects of the IFN-I pathway; they do not reflect the entirety of the pathway and some are not specific for IFN-I. The most appropriate assay will depend on the research or clinical question and should be justified.49.76±0.56
17 (100)
 3. Publications on novel IFN-I pathway assays should report whether they specifically reflect IFN-I, and to the extent possible, which IFN-I is measured.59.58±0.61
17 (100)
 4. For assays that evaluate pathways downstream of the IFN-I receptor (eg, IFN-stimulated gene expression or protein scores) the choice of components needs to be justified. For gene expression scores, the known subsets of IFN-stimulated genes should be described separately.59.41±0.87
16 (94.1)
 5. IFN-I pathway is consistently activated in several RMDs, but assays measuring IFN-I pathway activation cannot be currently recommended for diagnostic purposes.2b/3b8.58±1.83
12 (70.5)
 6. IFN-I pathway assays define more severe subgroups within many RMDs, so they should be considered in stratification studies.2b/3b8.70±1.31
12 (70.5)
 7. IFN-I pathway activation is associated with disease activity in some RMDs, especially SLE and myositis, but its added value in clinical decision making is uncertain.2b/3b8.82±1.18
14 (82.3)
 8. IFN-I pathway assays can predict disease exacerbations, in particular flare occurrence in patients with SLE, but further work should be performed to determine to what extent they outperform current instruments.2b9.00±1.00
16 (94.1)
 9. IFN-I pathway assays might predict progression from preclinical autoimmunity to clinical disease.2b8.00±1.69
11 (64.7)
 10. In SLE, IFN-I pathway assays may be useful in predicting response to IFN-I targeting therapies.2b8.76±1.20
14 (82.3)
 11. IFN-I pathway assay results may be affected by some treatments (eg, IFN-targeted therapies and high-dose glucocorticoids), and timing of sample collection should be taken into account and reported.2b/3b9.70±0.46
17 (100)

  • IFN-I, type I interferon; RMD, rheumatic and musculoskeletal disease; SLE, systematic literature review.