Brief Report: IFIH1 Mutation Causes Systemic Lupus Erythematosus With Selective IgA Deficiency

Arthritis & Rheumatology
Lien Van EyckAdrian Liston

Abstract

To identify the underlying genetic defect in a 16-year-old girl with severe early-onset and refractory systemic lupus erythematosus (SLE), IgA deficiency, and mild lower limb spasticity without neuroradiologic manifestations. Whole-exome sequencing and extensive immunologic analysis were performed on samples from the index patient. We identified a de novo p.R779H IFIH1 gain-of-function mutation in a patient with severe early-onset SLE, selective IgA deficiency, and mild lower limb spasticity. The same mutation in IFIH1 was recently identified in patients with Aicardi-Goutières syndrome, a rare neuroimmunologic disorder associated with elevated levels of type I interferon (IFN). IFN induced with helicase C domain 1 functions as an intracellular innate immune receptor that senses viral nucleic acids and leads to the induction of type I IFN and proinflammatory cytokines. Despite systemic immunosuppressive treatment, disease activity persisted in the patient and was associated with elevated serum levels of IFNα and up-regulation of IFIH1 itself. This finding adds a new genetic causation for Mendelian lupus and greatly extends the disease spectrum associated with mutations in IFIH1 (ranging from inflammatory encephalopathy to protot...Continue Reading

References

Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Feb 27, 2003·Proceedings of the National Academy of Sciences of the United States of America·Emily C BaechlerTimothy W Behrens
Jan 19, 2008·Journal of Clinical Immunology·Cristina M A JacobRenato C Monteiro
Jan 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael BonelliClemens Scheinecker
Aug 10, 2010·Nature Genetics·Ricardo C FerreiraLennart Hammarström
Nov 3, 2011·PLoS Genetics·Deborah S Cunninghame GrahamTimothy J Vyse
May 28, 2013·Immunity·Delphine GoubauCaetano Reis e Sousa
Aug 15, 2013·Current Rheumatology Reports·Patrícia Costa-Reis, Kathleen E Sullivan
Jan 1, 2014·American Journal of Medical Genetics. Part a·Roberta La PianaSimona Orcesi
Sep 23, 2014·Neuropediatrics·Yanick J CrowGillian I Rice

❮ Previous
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Citations

Jan 9, 2016·Zeitschrift für Rheumatologie·C GüntherM A Lee-Kirsch
Nov 5, 2015·Current Opinion in Immunology·Hiroki Kato, Takashi Fujita
Aug 12, 2015·Current Opinion in Immunology·Isabelle Melki, Yanick J Crow
Mar 20, 2016·Cytokine & Growth Factor Reviews·Insa BuersFrank Rutsch
Jun 24, 2015·Scandinavian Journal of Immunology·N Hagberg, L Rönnblom
Jul 22, 2015·Current Opinion in Rheumatology·Adriana Almeida de Jesus, Raphaela Goldbach-Mansky
Feb 29, 2016·Reumatología clinica·Francisco Rivas-Larrauri, Marco Antonio Yamazaki-Nakashimada
Jun 9, 2016·Expert Review of Clinical Immunology·Hassan AbolhassaniLennart Hammarström
Mar 24, 2017·International Reviews of Immunology·Daisuke OriTaro Kawai
Apr 16, 2017·The Journal of Biological Chemistry·Charlotte Lässig, Karl-Peter Hopfner
Jun 14, 2017·The Journal of Experimental Medicine·Ian T LambornHelen C Su
Aug 22, 2018·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Roli MandhanaCurt M Horvath
Mar 22, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Chen Seng NgTakashi Fujita
Jun 9, 2015·Nature Reviews. Immunology·Yanick J Crow, Nicolas Manel
Jan 24, 2019·Annual Review of Immunology·Sun Hur
May 18, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Sujin KimYoosik Kim
Jul 22, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chieri AkiyamaShunichi Shiozawa
Aug 2, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nobumasa SodaTakashi Fujita
Nov 9, 2016·The Journal of Experimental Medicine·Mathieu P Rodero, Yanick J Crow
Sep 22, 2016·Archivum Immunologiae Et Therapiae Experimentalis·Magdalena ZurawekJerzy Nowak
Jan 31, 2020·Cellular and Molecular Life Sciences : CMLS·Taisuke Nakahama, Yukio Kawahara
May 6, 2017·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Hiroki KatoTakashi Fujita
Jun 13, 2017·Arthritis & Rheumatology·Luciana Martins de CarvalhoYanick J Crow
Jun 9, 2020·Frontiers in Immunology·Shaoling ZhengTianwang Li
Mar 30, 2017·Clinical Science·Marc WeidenbuschHans-Joachim Anders
Feb 15, 2017·Cellular & Molecular Immunology·Ming-Ming Hu, Hong-Bing Shu
May 17, 2018·Rheumatology International·Ezgi Deniz Batu
Oct 12, 2017·Frontiers in Genetics·Maha ZakiHanno J Bolz
Nov 5, 2019·Frontiers in Immunology·Wenxiang SunSilvia Bolland
Oct 30, 2020·International Immunology·Ahmed Abu TayehTakashi Fujita
Nov 10, 2020·International Immunology·Hideo OnizawaTakashi Fujita
May 10, 2018·Allergologia et immunopathologia·S ZoghiN Rezaei
Nov 21, 2020·Signal Transduction and Targeted Therapy·Miaoqin ChenLifeng Feng
Jan 16, 2021·Viruses·Justine LagisquetThomas Gramberg
Feb 27, 2021·Frontiers in Immunology·Haruna OkudeTaro Kawai

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