Although ISG expression was higher in patients with known type I interferonopathies, patients with mutations in the gene RNASEH2B were more likely to have negative interferon signatures. Of the 8 patients with negative IS, seven had mutations in this particular gene. Additionally, the median interferon score in 26 patients positive for RNASEH2B mutations were lower than all of the other affected genes combined. 

Patients With Mutations RNASEH2

ISG expression levels were calculated in 82 patients with mutations in at least of the known AGS stimulated genes. The median value of each of the ISGs tested was objectively higher than the controls.A positive interferon score (>2.466) was recorded in 90% of patient samples compared to 7% of controls. Analysis of patient and control genotype displayed higher ISG expression median values compared with the controls. However, there isn’t a clear correlation between the extent of upregulation of specific ISGs according to genotype. 

Tulane University

The case-control study assessing interferon-related biomarkers in Aicardi-Goutières syndrome (AGS) yielded several key findings. An interferon signature was calculated, revealing that a positive interferon score (>$$ 2.466 $$) was recorded in $$ 90 $$ percent of patient samples compared to $$ 7 $$ percent of controls. Additionally, while patients with mutations in interferon-stimulated genes (ISGs) had higher median expression values, there was no clear correlation between the extent of upregulation, genotype, or patient age.

Results of Interferon Biomarker Assessment in AGS

Rice GI, Forte GM, Szynkiewicz M, Chase DS, Aeby A, Abdel-Hamid MS, Ackroyd S, Allcock R, Bailey KM, Balottin U, Barnerias C, Bernard G, Bodemer C, Botella MP, Cereda C, Chandler KE, Dabydeen L, Dale RC, De Laet C, De Goede CG, Del Toro M, Effat L, Enamorado NN, Fazzi E, Gener B, Haldre M, Lin JP, Livingston JH, Lourenco CM, Marques W Jr, Oades P, Peterson P, Rasmussen M, Roubertie A, Schmidt JL, Shalev SA, Simon R, Spiegel R, Swoboda KJ, Temtamy SA, Vassallo G, Vilain CN, Vogt J, Wermenbol V, Whitehouse WP, Soler D, Olivieri I, Orcesi S, Aglan MS, Zaki MS, Abdel-Salam GM, Vanderver A, Kisand K, Rozenberg F, Lebon P, Crow YJ. Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study. Lancet Neurol. 2013 Dec;12(12):1159-69. doi: 10.1016/S1474-4422(13)70258-8. Epub 2013 Oct 30. PMID: 24183309; PMCID: PMC4349523.

Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study

In order to calculate interferon levels in patients and controls, the expression of interferon stimulated genes (ISGs) need to be recorded using real time PCR. 6 interferon stimulated genes were analyzed and the corresponding probes were tagged to each sample in order to produce an interferon score. A positive interferon score was reported to be at least two standard deviations above the mean IFN signatures of the controls (>2-446). 

Calculating Interferon Signatures (IS)

IS Recorded in Patients w/mutations in ISGs

The data showed no clean correlation between the interferon score or genotype and age of patient. Eight patients who, at the time of sampling, were older than 20 years presented with a positive interferon score. The oldest patient was 32 years old and also presented with a positive interferon score. These results were interesting as age of onset of AGS is within 12 months of birth; however, the disease progresses early after onset of disease symptoms. There is not enough data to determine if an interferon signature can be related to severity of clinical phenotype. 

Learn Before

Related

Learn After