Type I interferon activation in RAS-associated autoimmune leukoproliferative disease (RALD).

Abstract

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.

• Authors: Riccardo Papa, Marta Rusmini, Francesca Schena, Elisabetta Traggiai, Maria Cristina Coccia, Roberta Caorsi, Serena Arrigo, Francesco Pasetti, Sara Signa, Patrizia Barone, Giuseppe Santamaria, Giovanni Spirito, Remo Sanges, Diego Vozzi, Andrea Cavalli, Stefano Gustincich, Angelo Ravelli, Marco Gattorno, Isabella Ceccherini, Stefano Volpi
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 231 Pg. 108837 (10 2021) ISSN: 1521-7035 [Electronic] United States
• PMID: 34455097 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Interferon Type I
• Membrane Proteins
• GTP Phosphohydrolases
• NRAS protein, human

Topics

• Adult
• Autoimmune Lymphoproliferative Syndrome (complications, genetics, immunology)
• GTP Phosphohydrolases (genetics)
• Humans
• Interferon Type I (immunology)
• Liver Diseases (genetics, immunology)
• Membrane Proteins (genetics)
• Mutation