IFN-signaling gene expression as a diagnostic biomarker for monogenic interferonopathies.
JCI Insight
; 9(14)2024 Jun 17.
Article
en En
| MEDLINE
| ID: mdl-38885315
ABSTRACT
IFN-signaling gene (ISG) expression scores are potential markers of inflammation with significance from cancer to genetic syndromes. In Aicardi Goutières Syndrome (AGS), a disorder of abnormal DNA and RNA metabolism, this score has potential as a diagnostic biomarker, although the approach to ISG calculation has not been standardized or validated. To optimize ISG calculation and validate ISG as a diagnostic biomarker, mRNA levels of 36 type I IFN response genes were quantified from 997 samples (including 334 AGS), and samples were randomized into training and test data sets. An independent validation cohort (n = 122) was also collected. ISGs were calculated using all potential combinations up to 6 genes. A 4-gene approach (IFI44L, IFI27, USP18, IFI6) was the best-performing model (AUC of 0.8872 [training data set], 0.9245 [test data set]). The majority of top-performing gene combinations included IFI44L. Performance of IFI44L alone was 0.8762 (training data set) and 0.9580 (test data set) by AUC. The top approaches were able to discriminate individuals with genetic interferonopathy from control samples. This study validates the context of use for the ISG score as a diagnostic biomarker and underscores the importance of IFI44L in diagnosis of genetic interferonopathies.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Biomarcadores
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Transducción de Señal
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Enfermedades Autoinmunes del Sistema Nervioso
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Malformaciones del Sistema Nervioso
Límite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
JCI Insight
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos