Encyclopedia of Medical Immunology

Living Edition
| Editors: Ian MacKay, Noel R. Rose

TIR Signaling Pathway Deficiency, HOIL1 Deficiency

  • Shan Yu Fung
  • Stuart E. Turvey
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-9209-2_48-1

Synonyms

Introduction

HOIL1 (Heme-Oxidized IRP2 Ubiquitin Ligase 1) deficiency is a novel, rare autosomal recessive disorder caused by biallelic disabling mutations in the gene HOIL1 (also known as RBCK1) with clinical characteristics of immunodeficiency, autoinflammation, and amylopectinosis. Currently, there are only three cases reported worldwide (Boisson et al. 2012). Patients with HOIL1 deficiency present recurrent pyogenic bacterial infections, episodes of noninfectious fever, autoinflammatory responses in the gastrointestinal tract and skin, hepatosplenomegaly, and glycogen storage dysfunction with amylopectin-like deposits in muscle tissues including cardiomyocytes. The detailed clinical manifestations are listed in Table 1.
Table 1

Clinical manifestations of HOIL1-deficient patients

Clinical manifestations

Family 1

Family 2

Patient 1 (compound heterozygous)

Patient 2 (compound heterozygous)

Patient 3 (homozygous)

Immunodeficiency

     

 Recurr...

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References

  1. Aksentijevich I, Zhou Q. NF-kappaB pathway in autoinflammatory diseases: dysregulation of protein modifications by ubiquitin defines a new category of autoinflammatory diseases. Front Immunol. 2017;8:399.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Boisson B, Laplantine E, Prando C, Giliani S, Israelsson E, Xu Z, et al. Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency. Nat Immunol. 2012;13(12):1178–86.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Boisson B, Laplantine E, Dobbs K, Cobat A, Tarantino N, Hazen M, et al. Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia. J Exp Med. 2015;212(6):939–51.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Casanova JL, Abel L, Quintana-Murci L. Human TLRs and IL-1Rs in host defense: natural insights from evolutionary, epidemiological, and clinical genetics. Annu Rev Immunol. 2011;29:447–91.CrossRefPubMedGoogle Scholar
  5. Ikeda F, Deribe YL, Skanland SS, Stieglitz B, Grabbe C, Franz-Wachtel M, et al. SHARPIN forms a linear ubiquitin ligase complex regulating NF-kappaB activity and apoptosis. Nature. 2011;471(7340):637–41.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Iwai K, Tokunaga F. Linear polyubiquitination: a new regulator of NF-kappaB activation. EMBO Rep. 2009;10(7):706–13.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Klein T, Fung SY, Renner F, Blank MA, Dufour A, Kang S, et al. The paracaspase MALT1 cleaves HOIL1 reducing linear ubiquitination by LUBAC to dampen lymphocyte NF-kappaB signalling. Nat Commun. 2015;6:8777.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Li Q, Verma IM. NF-kappaB regulation in the immune system. Nat Rev Immunol. 2002;2(10):725–34.CrossRefPubMedGoogle Scholar
  9. Oldfors A, DiMauro S. New insights in the field of muscle glycogenoses. Curr Opin Neurol. 2013;26(5):544–53.CrossRefPubMedGoogle Scholar
  10. Picard C, Casanova JL, Puel A. Infectious diseases in patients with IRAK-4, MyD88, NEMO, or IkappaBalpha deficiency. Clin Microbiol Rev. 2011;24(3):490–7.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Shimizu Y, Taraborrelli L, Walczak H. Linear ubiquitination in immunity. Immunol Rev. 2015;266(1):190–207.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Tokunaga F, Nakagawa T, Nakahara M, Saeki Y, Taniguchi M, Sakata S, et al. SHARPIN is a component of the NF-kappaB-activating linear ubiquitin chain assembly complex. Nature. 2011;471(7340):633–6.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2018

Authors and Affiliations

  • Shan Yu Fung
    • 1
  • Stuart E. Turvey
    • 1
  1. 1.BC Children’s Hospital Research Institute, University of British ColumbiaVancouverCanada

Section editors and affiliations

  • Stuart E Turvey
    • 1
  1. 1.British Columbia Children’s HospitalUniversity of British ColumbiaVancouverCanada