Hafize Emine Sönmez1, Cagatay Karaaslan2, Adriana A de Jesus3, Ezgi Deniz Batu1, Banu Anlar4, Betül Sözeri5, Yelda Bilginer1, Dilara Karaguzel2, Deniz Cagdas Ayvaz6, Ilhan Tezcan6, Raphaela Goldbach-Mansky3, Seza Ozen7. 1. Division of Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey. 2. Department of Biology, Molecular Biology Section, Hacettepe University Faculty of Science, Ankara, Turkey. 3. Translational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 4. Division of Neurology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey. 5. Division of Rheumatology, Department of Pediatrics, Umraniye Research and Training Hospital, Istanbul, Turkey. 6. Division of Immunology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey. 7. Division of Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey. sezaozen@gmail.com.
Abstract
OBJECTIVE: To develop a set of clinical criteria that identifies patients with a potential autoinflammatory IFNopathy. METHODS: Based on a literature review, a set of clinical criteria identifying genetically confirmed monogenic IFNopathies was selected. For validation, the clinical score was assessed in healthy controls (HCs) and 18 disease controls, including 2 known autoimmune IFNopathies, juvenile systemic lupus erythematosus (JSLE, n = 4) and dermatomyositis (JDM, n = 4); adenosine deaminase 2 deficiency (DADA2, n = 4); and oligoarticular juvenile idiopathic arthritis (oJIA, n = 6). We assessed an IFN score (IRG-S) in whole blood by NanoString using a previously published 28-gene-IRG-S and a reduced 6-gene-IRG-S. RESULTS: The 12 patients with a possible IFNopathy had higher clinical scores (3-5) than the patients with sJLE, JDM, DADA2, and oJIA and in HCs. Both the 28-IRG-S and 6-IRG-S were significantly higher in the autoinflammatory IFNopathy patients compared to HCs and oJIA and DADA2 patients but not different from patients with JSLE and JDM. Subsequently, genetic analysis revealed mutations in genes previously reported in genes related to the IFN pathway in 9 of the 12 patients. CONCLUSION: We developed a clinical score to identify patients with possible autoinflammatory IFNopathies. A clinical score was associated with a high IRG-S and may serve to identify patients with an autoinflammatory IFNopathy.
OBJECTIVE: To develop a set of clinical criteria that identifies patients with a potential autoinflammatory IFNopathy. METHODS: Based on a literature review, a set of clinical criteria identifying genetically confirmed monogenic IFNopathies was selected. For validation, the clinical score was assessed in healthy controls (HCs) and 18 disease controls, including 2 known autoimmune IFNopathies, juvenile systemic lupus erythematosus (JSLE, n = 4) and dermatomyositis (JDM, n = 4); adenosine deaminase 2 deficiency (DADA2, n = 4); and oligoarticular juvenile idiopathic arthritis (oJIA, n = 6). We assessed an IFN score (IRG-S) in whole blood by NanoString using a previously published 28-gene-IRG-S and a reduced 6-gene-IRG-S. RESULTS: The 12 patients with a possible IFNopathy had higher clinical scores (3-5) than the patients with sJLE, JDM, DADA2, and oJIA and in HCs. Both the 28-IRG-S and 6-IRG-S were significantly higher in the autoinflammatory IFNopathypatients compared to HCs and oJIA and DADA2 patients but not different from patients with JSLE and JDM. Subsequently, genetic analysis revealed mutations in genes previously reported in genes related to the IFN pathway in 9 of the 12 patients. CONCLUSION: We developed a clinical score to identify patients with possible autoinflammatory IFNopathies. A clinical score was associated with a high IRG-S and may serve to identify patients with an autoinflammatory IFNopathy.
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