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.

  • Article
  • Published:

Haematopoietic stem cell transplant for hyper-IgM syndrome due to CD40 defects: a single-centre experience

Bone Marrow Transplantation volume 54, pages 63–67 (2019)Cite this article

Subjects

Abstract

Hyper-IgM syndrome due to CD40 deficiency (HIGM3) is a rare disease with only a few reported cases of haematopoietic stem cell transplantation (HSCT). In retrospective study, we reviewed all patients with HIGM3 who underwent HSCT at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, between 2008 and 2013. Six patients were identified. Three male and three female patients from three families. The median age of diagnosis was 13 months (range, 1–28 months). All lacked CD40 expression on B cells by flow cytometry. The median time from diagnosis to transplantation was 8.5 months (range, 1–17 months). For all patients, the donors were HLA-identical siblings, with the exception of one patient for whom the donor was a sibling with one antigen mismatch. The conditioning regimen was busulfan and cyclophosphamide in five patients and busulfan, cyclophosphamide and antithymocyte globulin in one patient. For GVHD prophylaxis, cyclosporine and methotrexate was used. All patients engrafted. The survival rate was 100%, with a median follow-up of 54 months (range, 30–116 months). One patient developed acute GVHD. All patients showed complete immune recovery with positive CD40 expression on B cells and discontinued IVIG replacement. Our study shows that HSCT is potentially effective at curing the disease.

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

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

Similar content being viewed by others

References

  1. Ferrari S, Giliani S, Insalaco A, Al-Ghonaium A, Soresina A, Loubser M, et al. Mutations of CD40 gene cause an autosomal recessive form of immunodeficiency with hyper-IgM. Proc Natl Acad Sci USA. 2001;98:12614–19.

    Article  CAS  Google Scholar 

  2. Lougaris V, Badolato R, Ferrari S, Plebani A. Hyper immunoglobulin M syndrome due to CD 40 deficiency: clinical, molecular, and immunological features. Immunol Rev. 2005;203:48–66.

    Article  CAS  Google Scholar 

  3. Al-Saud BK, Al-Sum Z, Alassiri H, Al-Ghonaium A, Al-Muhsen S, Al-Dhekri H, Arnaout R, et al. Clinical, immunological, and molecular characterization of hyper-IgM syndrome due to CD40 deficiency in eleven patients. J Clin Immunol. 2013;33:1325–35.

    Article  CAS  Google Scholar 

  4. Kutukculer N, Aksoylar S, Kansoy S, Cetingul N, Notarangelo LD. Outcome of hematopoietic stem cell transplantation in hyper-IgM syndrome caused by CD40 deficiency. J Pediatr. 2003;143:141–42.

    Article  Google Scholar 

  5. Mazzolari E, Lanzi G, Forino C, Lanfranchi A, Aksu G, Ozturk C, et al. First successful stem cell transplantation in a child with CD40 deficiency. Bone Marrow Transplant. 2007;40:279–81.

    Article  CAS  Google Scholar 

  6. Al-Dhekri H, Al-Zum Z, Al-Saud B, Ayas M, Al-Muhsen S, Arnaout R, et al. Successful outcome in two patients with CD40 deficiency treated with allogeneic HCST. Clin Immunol. 2012;143:96–8.

    Article  CAS  Google Scholar 

  7. Leven EA, Maffucci P, Ochs HD, Scholl PR, Buckley RH, Fuleihan RL, et al. Hyper IgM syndrome: a report from the USIDNET registry. J Clin Immunol. 2016;36:490–501.

    Article  CAS  Google Scholar 

  8. Gathmann B, Grimbacher B, Beauté J, Dudoit Y, Mahlaoui N, Fischer A, et al. The European internet-based patient and research database for primary immunodeficiencies: results 2006–8. Clin Exp Immunol. 2009;157(Suppl 1):3–11.

    Article  Google Scholar 

  9. Fontana S, Moratto D, Mangal S, De Francesco M, Vermi W, Ferrari S, et al. Functional defects of dendritic cells in patients with CD40 deficiency. Blood. 2003;102:4099–106.

    Article  CAS  Google Scholar 

  10. Kutukculer N, Moratto D, Aydinok Y, Lougaris V, Aksoylar S, Plebani A, et al. Disseminated cryptosporidium infection in an infant with hyper-IgM syndrome caused by CD40 deficiency. J Pediatr. 2003;142:194–6.

    Article  Google Scholar 

  11. Karaca N, Forveille M, Aksu G, Durandy G, Kutukculer N. Hyper-immunoglobulin M syndrome type 3 with normal CD40 cell surface expression. Scand J Immunol. 2012;76:21–5.

    Article  CAS  Google Scholar 

  12. Mishra A, Italia K, Gupta M, Desai M, Madkaikar M. Hyperimmunoglobulin syndrome due to CD40 deficiency: possibly the first case from India. J Postgrad Med. 2015;61:46–8.

    Article  CAS  Google Scholar 

  13. O’Gorman MR, Zaas D, Paniagua M, Corrochano V, Scholl PR, Pachman LM. Development of a rapid whole blood flow cytometry procedure for the diagnosis of X-linked hyper-IgM syndrome. Clin Immunol Immunopathol. 1997;85:172–81.

    Article  Google Scholar 

  14. Qamar N, Fuleihan RL. The hyper IgM syndromes. Clin Rev Allergy Immunol. 2014;46:120–30.

    Article  CAS  Google Scholar 

  15. Levy J, Espanol-Boren T, Thomas C, Fischer A, Tovo P, Bordigoni P, et al. Clinical spectrum of X-linked Hyper-IgM syndrome. J Pediatr. 1997;131:47–54.

    Article  CAS  Google Scholar 

  16. de la Morena MT, Leonard D, Torgerson TR, Cabral-Marques O, Slatter M, Aghamohammadi A, et al. Long-term outcomes of 176 patients with X-linked hyper-IgM syndrome treated with or without hematopoietic cell transplantation. J Allergy Clin Immunol. 2017;139:1282–92.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, Section of Allergy and Immunology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

    B. Al-Saud, M. Al-Jomaie, A. Al-Ghonaium, H. Al-Mousa, S. Al-Muhsen, R. Arnaout, S. Elshorbagi & H. Al-Dhekri

  2. College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

    B. Al-Saud, A. Al-Ahmari, H. Al-Mousa & R. Arnaout

  3. Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

    A. Al-Ahmari, A. Al-Seraihy & M. Ayas

  4. King Saud University, Riyadh, Saudi Arabia

    S. Al-Muhsen

Authors
  1. B. Al-Saud
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Al-Jomaie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Al-Ghonaium
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Al-Ahmari
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. Al-Mousa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. Al-Muhsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Al-Seraihy
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. R. Arnaout
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S. Elshorbagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. H. Al-Dhekri
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. M. Ayas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to B. Al-Saud.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Al-Saud, B., Al-Jomaie, M., Al-Ghonaium, A. et al. Haematopoietic stem cell transplant for hyper-IgM syndrome due to CD40 defects: a single-centre experience. Bone Marrow Transplant 54, 63–67 (2019). https://doi.org/10.1038/s41409-018-0219-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-018-0219-0

This article is cited by

Search

Advanced search

Quick links