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Journal of Clinical Immunology

, Volume 39, Issue 2, pp 138–141 | Cite as

Auto-inflammation in a Patient with a Novel Homozygous OTULIN Mutation

  • Mohammad Nabavi
  • Mohammad Shahrooei
  • Hassan Rokni-Zadeh
  • Jeroen Vrancken
  • Majid Changi-Ashtiani
  • Kian Darabi
  • Mostafa Manian
  • Farhad Seif
  • Isabelle Meyts
  • Arnout Voet
  • Leen Moens
  • Xavier BossuytEmail author
Article

To the editor:

Homozygous mutations in OTULIN (Ovarian TUmor domain deubiquitinases with LINear linkage specificity) result in an auto-inflammation named OTULIN-related auto inflammatory syndrome (ORAS), characterized by prolonged recurrent fevers, joint swelling, gastrointestinal inflammation/diarrhea, failure to thrive, lipodystrophy, and painful erythematous rash with skin nodules [1, 2]. OTULIN deficiency manifests early in life and is potentially lethal.

OTULIN is a deubiquitinase that hydrolyzes linear ubiquitins [3]. Linear ubiquitination regulates various signaling pathways, including the NF-κB pathway. Ubiquitination of NEMO is mediated by Linear UBiquitin chain Assembly Complex (LUBAC). Patients with defects in a LUBAC component develop immunodeficiency and auto-inflammation and die in early childhood [4, 5]. OTULIN counter-regulates LUBAC activity by hydrolyzing linear ubiquitins, thereby avoiding unrestricted NF-κB activation. In the absence of OTULIN, the level of linear...

Notes

Acknowledgements

We kindly thank Saba Arshi, Mohammad Hassan Bemanian, Morteza Fallahpour, Alireza Nateghian, Farhad Abolhasan Chobdar, Davood Mansouri, Mehrnaz Mesdaghi, and Mojgan Kiani Amin for their cooperation and for their help in the work-up of the patient and taking care of the patient. We thank the patient and her family.

Research Funding

This work was supported by a Geconcerteerde Onderzoeksactie (GOA) grant from the Research Council of the Catholic University of Leuven, Belgium.

Authors’ Contribution

Whole-exome sequencing, data analysis, and clinical diagnosis were done by Mohammad Shahrooei, Hassan Rokni-Zadeh, and Majid Changi-Ashtiani. Kian Darabi collected the data, Mostafa Manian gathered samples for analyses, and Farhad Seif made substantial contributions to design of the study and edited the draft. Mohammad Nabavi took care of the patient. Isabelle Meyts edited the draft. Jeroen Vrancken and Arnout Voet performed and described the modeling studies. Leen Moens and Xavier Bossuyt designed the experimental studies. Leen Moens performed the experimental analyses. Mohammad Nabavi and Xavier Bossuyt drafted the manuscript. All authors read and approved the manuscript.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interests.

Ethical Approval

Informed consent was obtained.

Supplementary material

10875_2019_599_MOESM1_ESM.docx (198 kb)
ESM 1 (DOCX 197 kb).

References

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Mohammad Nabavi
    • 1
  • Mohammad Shahrooei
    • 2
    • 3
  • Hassan Rokni-Zadeh
    • 4
  • Jeroen Vrancken
    • 5
  • Majid Changi-Ashtiani
    • 6
  • Kian Darabi
    • 1
  • Mostafa Manian
    • 7
  • Farhad Seif
    • 7
    • 8
  • Isabelle Meyts
    • 3
    • 9
  • Arnout Voet
    • 5
  • Leen Moens
    • 3
  • Xavier Bossuyt
    • 3
    • 10
    Email author
  1. 1.Department of Allergy and Clinical ImmunologyIran University of Medical SciencesTehranIran
  2. 2.Specialized Immunology Laboratory of Dr. ShahrooeiAhvazIran
  3. 3.Department of Microbiology and ImmunologyKU LeuvenLeuvenBelgium
  4. 4.Department of Medical Biotechnology, School of MedicineZanjan University of Medical Sciences (ZUMS)ZanjanIran
  5. 5.Department of Chemistry Biochemistry, Molecular and Structural Biology SectionKU LeuvenLeuvenBelgium
  6. 6.School of MathematicsInstitute for Research in Fundamental Sciences (IPM)TehranIran
  7. 7.Department of Immunology, School of MedicineIran University of Medical SciencesTehranIran
  8. 8.Neuroscience Research CenterIran University of Medical SciencesTehranIran
  9. 9.Department of PediatricsUniversity Hospitals LeuvenLeuvenBelgium
  10. 10.Department of Laboratory MedicineUniversity Hospitals LeuvenLeuvenBelgium

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