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Journal of Clinical Immunology

, Volume 39, Issue 4, pp 353–357 | Cite as

IKZF1 Loss-of-Function Variant Causes Autoimmunity and Severe Familial Antiphospholipid Syndrome

  • Yannick Dieudonné
  • Aurélien Guffroy
  • Olivier Vollmer
  • Raphael Carapito
  • Anne-Sophie KorganowEmail author
Letter to the Editor

To the Editor,

Ikaros is a transcription factor with key roles in lymphocyte development and homeostasis. It is encoded by the IKAROS family zinc finger protein 1 (IKZF1) gene, which contains highly conserved N-terminal and C-terminal zinc finger domains and is highly expressed in hematopoietic cells. The functions of Ikaros were first illustrated in different sets of IKZF1-deficient mice. In humans, IKZF1 loss-of-function (LOF) somatic variants are associated with leukemogenesis in B cell acute lymphoblastic leukemia (B-ALL) [1]. More recently, different germline heterozygous variants, acting either by haploinsufficiency or by a dominant negative effect in IKZF1, were identified in autosomal dominant forms of common variable immunodeficiencies (CVID) or combined immunodeficiencies (CID) [2, 3, 4]. A series of families showed a progressive loss of B cells and hypogammaglobulinemia, but the absence of symptoms in several mutated patients suggests an incomplete penetrance. Additional...

Notes

Acknowledgments

We thank C. Bole and S. Hanein (Institut Imagine) for exome sequencing. We thank JL Pasquali and P Kieffer for clinical data. We thank S. Bahram for critical reading. We thank S Jung for her helpful comments.

Funding Information

A.S.K., A. G, and Y. D are supported by grants from the French Ministry of Health (PHRC IR 2011), from the Société Nationale Française de Médecine Interne (SNFMI), from the Hôpitaux Universitaires de Strasbourg (HUS), and from the EU-funded (ERDF) project INTERREG V “RARENET.” R.C. is supported by the Agence Nationale de la Recherche (ANR) (ANR-11-LABX-0070_TRANSPLANTEX), MSD Avenir, and the INTERREG V European regional development fund (European Union) program (project 3.2 TRIDIAG).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.

Supplementary material

10875_2019_643_MOESM1_ESM.docx (537 kb)
ESM 1 (DOCX 537 kb)

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Authors and Affiliations

  1. 1.CNRS UPR 3572, Immunopathology and Therapeutic Chemistry, Laboratory of Excellence MedalisInstitute of Molecular and Cellular Biology (IBMC)Strasbourg CedexFrance
  2. 2.Department of Clinical Immunology and Internal Medicine, National Reference Center for Autoimmune DiseasesHôpitaux Universitaires de StrasbourgStrasbourgFrance
  3. 3.UFR MédecineUniversité de StrasbourgStrasbourgFrance
  4. 4.Laboratoire d’ImmunoRhumatologie Moléculaire, plateforme GENOMAX, INSERM UMR_S 1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), LabEx TRANSPLANTEXUniversité de StrasbourgStrasbourgFrance
  5. 5.Service d’Immunologie Biologique, Plateau Technique de Biologie, Pôle de BiologieNouvel Hôpital CivilStrasbourgFrance

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