Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Single centre experience of haematopoietic SCT for patients with immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome

Bone Marrow Transplantation volume 49, pages 310–312 (2014)Cite this article

Subjects

Immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is an X-linked recessive disorder with mutations in FOXP3 causing absence of regulatory activity by CD4+CD25+ Foxp3+ regulatory T cells, which results in unchecked effector T-cell activation and mediating organ-specific autoimmunity.1 IPEX syndrome should be considered in any young male infant with intractable diarrhoea and/or gut villous atrophy and failure to thrive (FTT). Without treatment, many patients die in the first 2 years of life because of sepsis or FTT.2 Management of children with autoimmune enteropathy is challenging. Supportive care includes total parental nutrition (TPN), blood transfusions, treatment of autoimmune manifestations together with long-term immunosuppressive drug treatment, which may reduce clinical manifestations, but is not curative and drug toxicities limit this approach.3 Previous studies have shown that haematopoietic SCT (HSCT) is curative, however, side effects of conditioning or infections post transplant may be life-threatening, and early reports were unfavourable, with late death post transplantation described.4

We report five patients with IPEX syndrome and a confirmed mutation in FOXP3 who underwent HSCT between 2003 and 2010 at the Northern Supra-Regional Service for Paediatric Immunodeficiency in the United Kingdom. Clinical and laboratory data were collected from each patient’s medical case notes. Written consent was obtained from parents at the time of admission for HSCT.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Tsuda M, Torgerson TR, Selmi C, Gambineri E, Carneiro-Sampaio M, Mannurita SC et al. The spectrum of autoantibodies in IPEX syndrome is broad and includes anti-mitochondrial autoantibodies. J Autoimmun 2010; 35: 265–268.

    Article  CAS  Google Scholar 

  2. Gambineri E, Perroni L, Passerini L, Bianchi L, Doglioni C, Meschi F et al. Clinical and molecular profile of a new series of patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome: inconsistent correlation between forkhead box protein 3 expression and disease severity. J Allergy Clin Immunol 2008; 122: 1105–1112.

    Article  CAS  Google Scholar 

  3. Burroughs LM, Torgerson TR, Storb R, Carpenter PA, Rawlings DJ, Sanders J et al. Stable hematopoietic cell engraftment after low-intensity nonmyeloablative conditioning in patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. J Allergy Clin Immunol 2010; 126: 1000–1005.

    Article  CAS  Google Scholar 

  4. Wildin RS, Smyk-Pearson S, Filipovich AH . Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. J Med Genet 2002; 39: 537–545.

    Article  CAS  Google Scholar 

  5. Bacchetta R, Passerini L, Gambineri E, Dai M, Allan SE, Perroni L et al. Defective regulatory and effector T cell functions in patients with FOXP3 mutations. J Clin Invest 2006; 116: 1713–1722.

    Article  CAS  Google Scholar 

  6. Zhan H, Sinclair J, Adams S, Cale CM, Murch S, Perroni L et al. Immune reconstitution and recovery of FOXP3 (forkhead box P3)-expressing T cells after transplantation for IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome. Pediatrics 2008; 121: e998–1002.

    Article  Google Scholar 

  7. Lucas KG, Ungar D, Comito M, Bayerl M, Groh B . Submyeloablative cord blood transplantation corrects clinical defects seen in IPEX syndrome. Bone Marrow Transplant 2007; 39: 55–56.

    Article  CAS  Google Scholar 

  8. Seidel MG, Fritsch G, Lion T, Jurgens B, Heitger A, Bacchetta R et al. Selective engraftment of donor CD4+25high FOXP3-positive T cells in IPEX syndrome after nonmyeloablative hematopoietic stem cell transplantation. Blood 2009; 113: 5689–5691.

    Article  CAS  Google Scholar 

  9. Barzaghi F, Passerini L, Bacchetta R . Immune dysregulation, polyendocrinopathy, enteropathy, x-linked syndrome: a paradigm of immunodeficiency with autoimmunity. Front Immunol 2012; 3: 211.

    Article  Google Scholar 

  10. Rao A, Kamani N, Filipovich A, Lee SM, Davies SM, Dalal J et al. Successful bone marrow transplantation for IPEX syndrome after reduced-intensity conditioning. Blood 2007; 109: 383–385.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Paediatric Immunology, Newcastle upon Tyne Hospital Trust, Florence, Italy

    Z Nademi, M Slatter, S Hambleton, T Flood, A Cant, M Abinun & A Gennery

  2. Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK

    Z Nademi, M Slatter, S Hambleton, A Cant, M Abinun & A Gennery

  3. Paediatric Bone Marrow Transplant Unit, Florence, Italy

    E Gambineri & S C Mannurita

  4. Immunology laboratory, Newcastle upon Tyne Hospital Trust, Newcastle upon Tyne, UK

    D Barge

  5. Department of Paediatric Gastroenterology, Newcastle upon Tyne Hospital Trust, Newcastle upon Tyne, UK

    S Hodges, S Bunn & J Thomas

  6. Department of Cellular Pathology, Newcastle upon Tyne Hospital Trust, Newcastle upon Tyne, UK

    B Haugk

Authors
  1. Z Nademi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Slatter
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E Gambineri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S C Mannurita
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D Barge
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S Hodges
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S Bunn
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. B Haugk
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. S Hambleton
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. T Flood
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. A Cant
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. M Abinun
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. A Gennery
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Z Nademi.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nademi, Z., Slatter, M., Gambineri, E. et al. Single centre experience of haematopoietic SCT for patients with immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. Bone Marrow Transplant 49, 310–312 (2014). https://doi.org/10.1038/bmt.2013.181

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2013.181

This article is cited by

Search

Advanced search

Quick links