Objective:To establish the detection method for the interferon stimulated genes(ISGs), calculate the cut-off value and test it in clinical practice.Methods:Patients with type I interferonopathies who were admitted to Peking Union Medical College Hospital from November 2017 to September 2021 were chosen as the disease group, and healthy children were included as the control group. A total of 18 children were in the disease group, including 8 males and 10 females, with a median age of 8.5 years for the first test. From them 25 blood specimens were collected. A total of 28 healthy children, aged 1 to 18 years, with a median age of 10.5 years, including 15 males and 13 females, were included in the control group. Blood samples of 34 controls and 18 interferonopathies patients were collected, then total RNA extraction and cDNA synthesis were performed. Real-time quantitative polymerase chain reaction assays were run in duplicate to measure the expression of six ISGs: interferon induced protein with tetratricopeptide repeats 1 (IFIT1), interferon α inducible protein 27 (IFI27), interferon induced protein 44 like (IFI44L), interferon stimulated genes 15 (ISG15), sialic acid binding Ig like lectin 1 (SIGLEC1), and radical S-adenosyl methionine domain containing 2 (RSAD2). The relative abundances of each target transcript was normalized to the expression level of β-Actin and OAZ. The median fold change of the six ISGs was used to create an interferon score (IS) for each individual. Samples with abnormal expressions were removed and the cDNA mix of the remaining samples was used as a calibrator to calculate the IS. We define an abnormal IS as being greater than+2 standard deviations above the mean of controls. Differences in IS between groups were compared using t-test or Mann-Whitney U-test. Results:The mean IS of controls was 1.046, standard 0.755, and the cut-off value was 2.556. A total of 25 samples from 18 interferonopathies patients were tested. The mean value was 27.010 with a 15/18 abnormality rate. Compared with the control group, IS in patients was significantly higher, t=4.247( P=0.000 1). The accuracy, precision, sensitivity, and specificity were 91.30% (42/46), 7.47%(0.084/1.124), 15/18, and 96.43% (27/28), respectively. Conclusion:This study provides a new and reliable method for clinical screening and dynamic monitoring of type Ⅰ interferonopathies by detecting ISGs expression and creating an IS.

Objective:To summarize the clinical characteristics of type I interferonopathies and provide clues for early identification and diagnosis.Methods:Clinical data of 20 patients admitted to Department of Pediatrics, Peking Union Medical College Hospital and 5 patients admitted to Department of Rheumatology and Immunology, Shenzhen Children′s Hospital from January 2016 to September 2021 were retrospectively analyzed. The data included gene results, clinical manifestations and auxiliary examination results.Results:Of the 25 cases, 12 were males and 13 were females. Age of onset ranged from 1 day to 11 years. And 84% of them had the onset before the age of 3 years. The cases consisted of 14 cases of Aicardi-Goutières syndrome (AGS), 6 cases of adenosine deaminase 2 deficiency (DADA2), 3 cases of stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI), and 2 cases of Spondyloenchondrodysplasia with immune dysregulation (SPENCDI). Eighteen patients (72%) experienced neurologic disorder, among whom 16 (64%) showed intracranial calcification, 11 (44%) had dystonia, 10 (40%) had leukodystrophy, 6 (24%) had epilepsy, 5 (20%) had brain atrophy and 5 (20%) had early-onset cerebrovascular events. Skin involvement occurred in 15 cases (60%), among whom 8 cases (32%) had chilblain-like rash, 4 cases (16%) had livedo reticularis, 3 cases (12%) had erythema, 2 cases (8%) had erythema nodosum and 2 cases (8%) had Raynaud′s phenomenon. In addition, 12 cases (48%) had positive autoimmune antibodies, 10 cases (40%) manifested as developmental retardation, 8 cases (32%) experienced lung interstitial lesions, and 7 cases (28%) demonstrated thyroid dysfunction. And 1 died (4%) at 11 years of age.Conclusions:Type Ⅰinterferonopathies can involve multiple organs, and share the characteristics of systemic inflammatory and autoimmune diseases. The early-onset neurological symptoms (early-onset cerebrovascular events, intracranial calcification, leukodystrophy and cerebral atrophy), rashes (chilblain-like rash, livedo reticularis and erythema), positive autoimmune antibodies, developmental delay, interstitial lung disease and thyroid dysfunction may indicate type Ⅰ interferonopathies.