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Introduction: Interferon I (IFN I) signaling hyperactivation is considered one of the most important pathogenetic mechanisms in systemic lupus erythematosus (SLE). Early manifestation and more severe SLE courses in children suggest a stronger genetic influence in childhood-onset SLE (cSLE). Aim: To evaluate IFN-I score and SLE-associated genetic variants in cSLE. Material and Methods: 80 patients with cSLE were included in the study. IFN I-score was assessed by real-time PCR quantitation of 5 IFN I-regulated transcripts (IFI44L, IFI44, IFIT3, LY6E, MXA1) in 60 patients. Clinical exome sequencing (CES) was performed in 51 patients. Whole-exome sequencing was performed in 32 patients with negative results of CES. Results: 46/60 patients (77%) had elevated IFN-I scores. Leucopenia and skin involvement were associated with over-expression of IFI44 and IFI44L, while hypocomplementemia—with hyperactivation of IFIT3, LY6E, and MX1. No correlation of IFN-I score with disease activity was found. At least one rare genetic variant, potentially associated with SLE, was found in 29 (56.9%) patients. The frequency of any SLE-genetic variants in patients with increased IFN scores was 84%, in patients with normal IFN scores—33%, and in the group whose IFN score was not assessed was 65% (p = 0.040). The majority of genetic variants (74%) are functionally related to nucleic acid sensing and IFN-signaling. The highest frequency of genetic variants was observed in Sakha patients (9/14; 64.3%); three and two unrelated patients had identical variants in PTPN22 and TREX1 genes, respectively. Conclusions: More than half of patients with childhood-onset SLE have rare variants in SLE-associated genes. The IFN-I score could be considered a tool for the selection of patients for further genetic assessment in whom monogenic lupus is suspected. [ABSTRACT FROM AUTHOR]

Introduction: Aicardi-Gouteres syndrome (AGS) is a monogenic interferonopathy characterized by early onset, dysregulation of skin (chilblain lesions), brain, and immune systems (fever, hepatomegaly, glaucoma, arthritis, myositis, and autoimmune activity). The disease looks like TORCH (Toxoplasmosis, Others, Rubella, Cytomegalovirus, Herpes) infection with early-onset encephalopathy resulting in severe neuropsychological disability. Case description: A six-year-old girl has been suffering from generalized seizures, fever episodes, severe psychomotor development delay, and spastic tetraparesis since the first year of her life. Her two elder brothers died at a young age from suspected infantile cerebral palsy (ICP). Other siblings (younger brother and two elder sisters) are as healthy as their parents. The girl was diagnosed with juvenile dermatomyositis at 5.5 years. Basal ganglia, periventricular, and cerebellum calcifications; hypoplasia of the corpus callosum; and leukodystrophy were detected on CT. The IFN-I score was 12 times higher than normal. The previously not described nucleotide variant c.434G > C (chr 20:36935104C > G; NM_015474) was detected in exon 4 of the SAMHD1 gene in the homozygous state, leading to amino acid substitution p.R145P. Aicardi-Goutières syndrome 5 was diagnosed. Her treatment included corticosteroids, methotrexate, and tofacitinib 5 mg twice a day and it contributed to health improvements. The following brain CT depicted the previously discovered changes without the sign of calcification spreading. Conclusions: Early diagnosis of AGS is highly important as it allows starting treatment in a timely manner. Timely treatment, in return, can help avoid the development/progression of end-organ damage, including severe neurological complications and early death. It is necessary to spread information about AGS among neurologists, neonatologists, infectious disease specialists, and pediatricians. A multidisciplinary team approach is required. [ABSTRACT FROM AUTHOR]

Background/Objectives: Cervical spine arthritis (CSA) in children with juvenile idiopathic arthritis (JIA) can lead to clinically significant and irreversible functional impairment. Our study aimed to evaluate the features of the JIA disease course in children with CSA. Methods: In the retrospective cohort study, the data from medical charts of children with JIA (n = 753) who corresponded to the ILAR criteria and were treated from 2007 to 2016 were included. CSA was diagnosed by clinical manifestations (pain and limited range of motion) with radiological confirmation in the available cases. Results: CSA had 101 JIA patients (13.4%), predominantly with polyarticular (48%, OR = 1.8 (1.2; 2.7), p < 0.001) and systemic (18.9%, OR = 3.6 [2.0; 6.6], p < 0.001) JIA categories. CSA was associated with longer disease duration, higher inflammatory activity, a higher number of active joints, a lower probability of achieving remission (HR = 1.33 (95% CI: 1.01; 1.76, p = 0.04)), and a higher probability of being treated with biologics (HR = 1.78 (95% CI: 1.22; 2.59, p = 0.002)). Patients with temporomandibular arthritis (OR = 10.4 [5.4; 19.8], p < 0.001) and shoulder arthritis (OR = 14.1 [7.5; 26.3], p < 0.001) had the highest risk of having CSA. Conclusions: CSA was an independent predictor of treatment with biologics and failure to achieve remission. Identified predictors can help to find the group of patients with higher suspicion for whom the functional tests and MRI are required to not miss the CSA. A radiology assessment of CSA should be performed as far as possible in children, unless there are risks of general anesthesia for younger patients.