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. 2025 Jan 21;219(1):uxaf018.
doi: 10.1093/cei/uxaf018.

Type I interferon signature: a quantitative standardized method for clinical application

Alessandra Tesser  1 , Paola Bocca  2 , Massimo Ulivi  3 , Alessia Pin  1 , Claudia Pastorino  2 , Davide Cangelosi  4 , Elettra Santori  5 , Enrico Drago  2   6 , Roberta Caorsi  2 , Fabio Candotti  5 , Marco Gattorno  2 , Alberto Tommasini  1   7 , Stefano Volpi  2   6
Affiliations

Type I interferon signature: a quantitative standardized method for clinical application

Alessandra Tesser et al. Clin Exp Immunol. .

Abstract

Type I Interferon (IFN) induced gene expression analysis ("IFN signature") is employed to categorize pathological conditions that exhibit Type I IFN dysregulation and to direct customized therapeutic strategies. For instance, it is used to differentiate patients with IFN-related inflammation from those with conditions primarily mediated by other cytokines, such as juvenile idiopathic arthritis and periodic fevers. Nevertheless, there is currently no standardized method available for clinical practice, and comparing values at different time points or between centers poses a challenge. In this work, we described a standardized method based on the development and validation of a synthetic control to solve the problem of test comparison. Inter-assay and inter-laboratory variability were assessed by multiple repeated analyses within the same laboratory, and between two different laboratories involved in the study. The method has been validated by evaluating the IFN signature of 39 patients with inflammatory disorders known to be related or not to Type I IFN (i.e. monogenic interferonopathies, systemic lupus erythematosus, juvenile dermatomyositis, periodic fevers, and juvenile idiopathic arthritis). The proposed method proved to be highly reproducible among centers and able to discriminate among IFN-related or non-IFN-related inflammation. The use of a synthetic control minimized the inter-assay and inter-laboratory variability, and thus facilitate data sharing among centers to improve knowledge of IFN-related inflammation and patient's care.

Keywords: data comparison; interferon inflammation; interferon signature; patient classification; standardized method.

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Figures

Graphical Abstract
Graphical Abstract
Figure 1:
Figure 1:
inter-assay variability of the synthetic control (106, 104, and 102 copies). The graph shows the analysis for each of the eight genes (Ct: cycle threshold)
Figure 2:
Figure 2:
inter-laboratory variability of the synthetic control (106, 104, and 102 copies) between U1 and U2. The graph shows the analysis for each of the eight genes (Ct: cycle threshold)
Figure 3:
Figure 3:
IFN score cut-off value (0.66) was calculated on 40 healthy donors (HD) as the mean + 2 standard deviations of the HD’s IFN scores (dashed line)
Figure 4:
Figure 4:
inter-laboratory comparison of gene scores (GS) of the eight genes calculated in U1 and U2 for the same four patients with juvenile systemic lupus erythematosus (JSLE) and three patients with juvenile dermatomyositis (JDM)
Figure 5:
Figure 5:
inter-laboratory comparison of IFN scores calculated in U1 and U2 of the same subjects (4 healthy donors and 7 patients). The dashed line represents the cut-off value
Figure 6:
Figure 6:
IFN score of 40 healthy donors (HD) and 39 patients with different inflammatory conditions: N = 8 with juvenile systemic lupus erythematosus (JSLE), N = 9 with juvenile dermatomyositis (JDM), N = 7 with Type 1 interferonopathy (T1I), N = 7 with periodic fevers (PF), N = 8 with juvenile idiopathic arthritis (JIA). The dashed line represents the cut-off value (0.66)
See this image and copyright information in PMC

References

    1. Stetson DB, Medzhitov R.. Type I interferons in host defense. Immunity 2006, 25, 373–81. doi: https://doi.org/10.1016/j.immuni.2006.08.007 - DOI - PubMed
    1. Isaacs A, Lindenmann J.. Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci 1957, 147, 258–67. doi: https://doi.org/10.1098/rspb.1957.0048 - DOI - PubMed
    1. Hooks JJ, Moutsopoulos HM, Geis SA, Stahl NI, Decker JL, Notkins AL.. Immune interferon in the circulation of patients with autoimmune disease. N Engl J Med 1979, 301, 5–8. doi: https://doi.org/10.1056/NEJM197907053010102 - DOI - PubMed
    1. Yao Y, Higgs BW, Richman L, White B, Jallal B.. Use of type I interferon-inducible mRNAs as pharmacodynamic markers and potential diagnostic markers in trials with sifalimumab, an anti-IFNα antibody, in systemic lupus erythematosus. Arthritis Res Ther 2010, 12, S6. doi: https://doi.org/10.1186/ar2887 - DOI - PMC - PubMed
    1. Crow YJ, Black DN, Ali M, Bond J, Jackson AP, Lefson M, et al.Cree encephalitis is allelic with Aicardi–Goutiéres syndrome: implications for the pathogenesis of disorders of interferon alpha metabolism. J Med Genet 2003, 40, 183–7. doi: https://doi.org/10.1136/jmg.40.3.183 - DOI - PMC - PubMed

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