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A Report of Novel STIM1 Deficiency and 6-Year Follow-Up of Two Previous Cases Associated with Mild Immunological Phenotype

  • Laura Rice
  • Claire Stockdale
  • Ian Berry
  • Sean O’Riordan
  • Karen Pysden
  • Rashida Anwar
  • Roger Rushambuza
  • Moira Blyth
  • Sonal Srikanth
  • Yousang Gwack
  • Yasser M. El-Sherbiny
  • Clive Carter
  • Sinisa SavicEmail author
Letter to Editor

To the Editor,

Loss of function or null mutations of stromal interaction molecule 1 (STIM1) are known to cause early-onset combined immunodeficiency (CID) disease with recurrent and chronic infections, autoimmunity, haemolytic anemia, ectodermal dysplasia, muscular weakness, and myalgia [1]. STIM1 and ORAI1 form the calcium release-activated calcium (CRAC) channels and are involved in calcium signaling, which is especially important in T cells for activation, proliferation, and cytokine production [2]. ORAI1 forms the pore in the plasma membrane, and STIM1 is a calcium sensor protein that activates the ORAI1 when the endoplasmic reticulum (ER) Ca2+ stores are depleted.

STIM1-deficient patients have impaired T cells and NK cell function, but usually a normal distribution of the major immune cell types, including T cells, B cells, and natural killer (NK) cells with the T cell repertoire that is normally comparable with healthy individuals [3]. STIM1 deficiency results in no...

Notes

Funding

This research is supported by a grant from the CSL Behring and by the National Institute for Health Research (NIHR) Leeds Biomedical Research Centre.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Disclaimer

The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.

Supplementary material

10875_2019_618_MOESM1_ESM.docx (148 kb)
ESM 1 (DOCX 147 kb)
10875_2019_618_Fig5_ESM.png (369 kb)
Supplementary Figure 1

TCR repertoire as assessed by T receptor spectra phenotyping. The arrow is showing a missing Vb7.2 expression on patients’ T cells. (PNG 368 kb)

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High resolution image (TIFF 5331 kb)
10875_2019_618_Fig6_ESM.png (590 kb)
Supplementary Figure 2

A) Phytohaemagglutinin (PHA, 3 differed concentrations 5,10 and 100 μg/ml) and anti-CD3 T cell proliferation (P1 red 2 separate experiments) Healthy controls (HC black) X3 B) CD69, HLA-DR and CD25 expression on T cells from the patient (P1 red) and 3 HC black following stimulation with anti-CD3 for 48 h (PNG 590 kb)

10875_2019_618_MOESM3_ESM.tiff (5.2 mb)
High resolution image (TIFF 5331 kb)

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Copyright information

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

Authors and Affiliations

  • Laura Rice
    • 1
  • Claire Stockdale
    • 2
  • Ian Berry
    • 3
  • Sean O’Riordan
    • 4
  • Karen Pysden
    • 5
  • Rashida Anwar
    • 1
  • Roger Rushambuza
    • 6
  • Moira Blyth
    • 3
  • Sonal Srikanth
    • 7
  • Yousang Gwack
    • 7
  • Yasser M. El-Sherbiny
    • 8
    • 9
    • 10
  • Clive Carter
    • 2
  • Sinisa Savic
    • 2
    • 10
    Email author
  1. 1.Leeds Institute of Medical Research at St James’s, Wellcome Trust Brenner Building, St James’s University HospitalUniversity of LeedsLeedsUK
  2. 2.Department of Clinical Immunology and AllergySt James’s University HospitalLeedsUK
  3. 3.Yorkshire Regional Genetics ServiceChapel Allerton HospitalLeedsUK
  4. 4.Department of Paediatric ImmunologyLeeds General InfirmaryLeedsUK
  5. 5.Department of Paediatric NeurologyLeeds General InfirmaryLeedsUK
  6. 6.Department of RadiologyCalderdale and Huddersfield NHS Foundation TrustHuddersfieldUK
  7. 7.Department of Physiology, David Geffen School of MedicineUCLALos AngelesUSA
  8. 8.Department of Biosciences, School of Science and TechnologyNottingham Trent UniversityNottinghamUK
  9. 9.Clinical Pathology Department, Faculty of MedicineMansoura UniversityMansouraEgypt
  10. 10.National Institute for Health Research—Leeds Biomedical Research Centre and Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM), Wellcome Trust Brenner BuildingSt James’s University HospitalLeedsUK

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