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


Journal

Clinical immunology (Orlando, Fla.)
ISSN: 1521-7035
Titre abrégé: Clin Immunol
Pays: United States
ID NLM: 100883537

Informations de publication

Date de publication:
10 2021
Historique:
received: 04 06 2021
revised: 13 08 2021
accepted: 23 08 2021
pubmed: 30 8 2021
medline: 10 11 2021
entrez: 29 8 2021
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 34455097
pii: S1521-6616(21)00174-1
doi: 10.1016/j.clim.2021.108837
pii:
doi:

Substances chimiques

Interferon Type I 0
Membrane Proteins 0
GTP Phosphohydrolases EC 3.6.1.-
NRAS protein, human EC 3.6.1.-

Types de publication

Case Reports Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

108837

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Auteurs

Riccardo Papa (R)

Center for Autoinflammatory Diseases and Immunodeficiencies, IRCCS Istituto Giannina Gaslini, Genoa, Italy; DINOGMI, Università di Genova, Genoa, Italy.

Marta Rusmini (M)

Laboratory of Genetics and Genomics of Rare Diseases, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Francesca Schena (F)

Center for Autoinflammatory Diseases and Immunodeficiencies, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Elisabetta Traggiai (E)

Novartis Institutes for Biomedical Research, Basel, Switzerland.

Maria Cristina Coccia (MC)

Unit of Pathology, Department of Translational Research, Laboratory Medicine, Diagnostics and Services, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Roberta Caorsi (R)

Center for Autoinflammatory Diseases and Immunodeficiencies, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Serena Arrigo (S)

Pediatric Gastroenterology and Endoscopy Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Francesco Pasetti (F)

Interventional Radiology and Neuroradiology Unit, Istituto G Gaslini, Genoa, Italy.

Sara Signa (S)

Center for Autoinflammatory Diseases and Immunodeficiencies, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Patrizia Barone (P)

Department of Pediatrics, University of Catania, Catania, Italy.

Giuseppe Santamaria (G)

Laboratory of Genetics and Genomics of Rare Diseases, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Giovanni Spirito (G)

Area of Neurobiology, SISSA, Trieste, Italy.

Remo Sanges (R)

Area of Neurobiology, SISSA, Trieste, Italy.

Diego Vozzi (D)

RNA Central Lab, IIT, Genova, Italy.

Andrea Cavalli (A)

RNA Central Lab, IIT, Genova, Italy.

Stefano Gustincich (S)

RNA Central Lab, IIT, Genova, Italy.

Angelo Ravelli (A)

DINOGMI, Università di Genova, Genoa, Italy; Clinica Pediatrica e Reumatologia, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Marco Gattorno (M)

Center for Autoinflammatory Diseases and Immunodeficiencies, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Isabella Ceccherini (I)

Laboratory of Genetics and Genomics of Rare Diseases, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Stefano Volpi (S)

Center for Autoinflammatory Diseases and Immunodeficiencies, IRCCS Istituto Giannina Gaslini, Genoa, Italy; DINOGMI, Università di Genova, Genoa, Italy. Electronic address: stefanovolpi@gaslini.org.

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Classifications MeSH