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.

Type I interferon activation in RAS-associated autoimmune leukoproliferative disease (RALD) / Pa, pa R.; Rusmini, M.; Schena, F.; Traggiai, E.; Coccia, M. C.; Caorsi, R.; Arrigo, S.; Pasetti, F.; Signa, S.; Barone, P.; Santamaria, G.; Spirito, G.; Sanges, R.; Vozzi, D.; Cavalli, A.; Gustincich, S.; Ravelli, A.; Gattorno, M.; Ceccherini, I.; Volpi, S.. - In: CLINICAL IMMUNOLOGY. - ISSN 1521-6616. - 231:(2021). [10.1016/j.clim.2021.108837]

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

Spirito, G.
Membro del Collaboration group
;
Sanges, R.
Membro del Collaboration group
;
Gustincich, S.
Membro del Collaboration group
;
2021-01-01

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.
231
108837
Pa, pa R.; Rusmini, M.; Schena, F.; Traggiai, E.; Coccia, M. C.; Caorsi, R.; Arrigo, S.; Pasetti, F.; Signa, S.; Barone, P.; Santamaria, G.; Spirito, G.; Sanges, R.; Vozzi, D.; Cavalli, A.; Gustincich, S.; Ravelli, A.; Gattorno, M.; Ceccherini, I.; Volpi, S.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11767/127673
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 1
  • ???jsp.display-item.citation.isi??? 0
social impact