Type I interferon activation in RAS-associated autoimmune leukoproliferative disease (RALD)
| Autor: | Giovanni Spirito, Roberta Caorsi, Stefano Volpi, Sara Signa, Stefano Gustincich, Remo Sanges, Francesco Pasetti, Francesca Schena, Isabella Ceccherini, Patrizia Barone, Marta Rusmini, Riccardo Papa, Elisabetta Traggiai, Andrea Cavalli, Maria C Coccia, Angelo Ravelli, Giuseppe Santamaria, Diego Vozzi, Serena Arrigo, Marco Gattorno |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Neuroblastoma RAS viral oncogene homolog
Adult Interferon NRAS RALD Regenerative nodular hyperplasia SLE Autoimmune Lymphoproliferative Syndrome GTP Phosphohydrolases Humans Interferon Type I Liver Diseases Membrane Proteins Mutation Immunology Gene mutation medicine.disease_cause Hypogammaglobulinemia Immunology and Allergy Medicine Hepatopulmonary syndrome Exome sequencing business.industry Immune dysregulation medicine.disease Settore FIS/07 - Fisica Applicata(Beni Culturali Ambientali Biol.e Medicin) KRAS business medicine.drug |
| Popis: | RAS-associated autoimmune leukoproliferative disease (RALD) is a rare immune dysregulation syndrome caused by somatic gain-of-function mutations of either NRAS or KRAS gene in hematopoietic cells. We describe a 27-year-old patient presenting at 5 months of age with recurrent infections and generalized lymphadenopathy who developed a complex multi-organ autoimmune syndrome with hypogammaglobulinemia, partially controlled with oral steroids, hydroxichloroquine, mofetil mycophenolate and IVIG prophylaxis. Activation of type I interferon pathway was observed in peripheral blood. Since 18 years of age, the patient developed regenerative nodular hyperplasia of the liver evolving into hepatopulmonary syndrome. Whole exome sequencing analysis of the peripheral blood DNA showed the NRAS p.Gly13Asp mutation validated as somatic. Our report highlights the possibility of detecting somatic NRAS gene mutations in patients with inflammatory immune dysregulation and type I interferon activation. |
| Databáze: | OpenAIRE |
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