Type 1 Interferon‐Stimulated Gene Expression and Disease Activity in Pediatric Rheumatic Diseases: No Composite Scores Needed?

Autor:	Weiden, Christina, Saers, Melanie, Schwarz, Tobias, Hinze, Tanja, Wittkowski, Helmut, Kessel, Christoph, Masjosthusmann, Katja, Mohr, Michael, Evers, Georg, Oesingmann‐Weirich, Sandra, Foell, Dirk, Hinze, Claas H.
Předmět:	INTERLEUKINS REVERSE transcriptase polymerase chain reaction DERMATOMYOSITIS PEDIATRICS INTERFERONS GENE expression RHEUMATISM in children GENE expression profiling DESCRIPTIVE statistics CHI-squared test SYSTEMIC lupus erythematosus DATA analysis software STATISTICAL correlation RECEIVER operating characteristic curves
Zdroj:	ACR Open Rheumatology; Dec2023, Vol. 5 Issue 12, p652-662, 11p
Abstrakt:	Objective: Rheumatic diseases are characterized by different patterns of immune overactivation. This study investigated the correlation of whole blood type 1 interferon (IFN) stimulated gene (ISG), IL18, and CXCL9 expression with clinical disease activity in pediatric rheumatic diseases and assessed the required number of ISGs to be included in a composite type 1 IFN score. Methods: Whole blood‐derived RNA and clinical data were collected from 171 mostly pediatric patients with connective tissue diseases (CTDs), systemic autoinflammatory diseases (SAIDs), monogenic interferonopathies (IFNPs) and other inflammatory diseases, and from 38 controls. The expression of six previously established ISGs, IL18, and CXCL9 was assessed by real‐time polymerase chain reaction (471 samples). Individual and composite gene expression was assessed, and correlation and threshold analyses were performed. Results: Correlation between ISG expression and clinical disease activity was strongest in CTD, especially in juvenile dermatomyositis (JDM) and IFNP, and modest in patients with SAID. Threshold ISG expression levels for the detection of at least mild clinical disease activity were substantially higher in patients with systemic lupus erythematosus compared with JDM. The correlation of expression levels of limited sets of ISGs and even individual ISGs with clinical disease activity were not inferior to a composite score of six ISGs. Conclusion: In a real‐world cohort, individual ISG expression levels robustly reflected clinical disease activity in CTD and IFNP, especially in JDM, which would simplify such analyses in clinical routine and be more cost‐effective. Threshold levels varied across diseases, potentially reflecting different mechanisms of type 1 IFN overactivation. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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