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First report of successful stem cell transplantation in a child with CD40 deficiency

Bone Marrow Transplantation volume 40, pages 279–281 (2007)Cite this article

CD40 deficiency is a rare form of autosomal recessive combined immunodeficiency, caused by mutations in the TNFRSF5 gene.1, 2 The CD40 transmembrane protein is constitutively expressed by B lymphocytes, monocytes and dendritic cells (DCs), but can also be expressed by some non-immune cells, such as endothelial and neuronal cells. Interaction between CD40-expressing B lymphocytes and activated CD4+ T cells that express CD40 ligand (CD40L) promotes B cell proliferation, triggers class-switch recombination and somatic hypermutation, and induces generation of long-lived plasma cells.3 Moreover, CD40L/CD40 interaction between activated T cells and DCs is essential to promote T cell priming and interferon-γ secretion and thus to defend against intracellular pathogens.4 Accordingly, patients with CD40 or with CD40L deficiency share a common and severe phenotype. They have reduced levels of all immunoglobulin isotypes other than IgM, and present with recurrent bacterial and opportunistic infections.1, 5 Moreover, they tend to develop severe neutropenia, which further contributes to susceptibility to infections. In the view of the severe manifestations and outcome associated with defects of the CD40L/CD40 axis, hematopoietic stem cell transplantation (HSCT) has been successfully used to cure CD40L deficiency.6 However, such strategy has been attempted only once, and unsuccessfully, in CD40 deficiency.7 In addition to clinical status at transplantation, and previous infection by Pneumocystis jiroveci and Cryptosporidium parvum, that represent negative prognostic factors for patients with CD40L or with CD40 deficiency,6, 7 additional concerns have been raised on the potential efficacy of HSCT for CD40 deficiency, including the need of myeloablation to reconstitute the myeloid compartment, and inability to correct CD40 deficiency in non-hematopoietic cells.

We report here on the first case in which successful immune reconstitution has been achieved in a child with CD40 deficiency following myeloablative HSCT from her HLA-identical sister.

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References

  1. Ferrari S, Giliani S, Insalaco A, Al-Ghonaium A, Soresina AR, 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: 12614–12619.

    Article  CAS  Google Scholar 

  2. Notarangelo LD, Lanzi G, Peron S, Durandy A . Defects of class-switch recombination. J Allergy Clin Immunol 2006; 117: 855–864.

    Article  CAS  Google Scholar 

  3. Geha RS, Plebani A, Notarangelo LD . CD40, CD40 ligand and the hyper-IgM syndrome. In: Ochs HD, Smith CIE, Puck JM (eds). Primary Immunodeficiency Diseases. A Molecular and Genetic Approach, 2nd edn. Oxford University Press: Philadelphia, PA, 2007, pp 251–268.

    Google Scholar 

  4. 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: 4099–4106.

    Article  CAS  Google Scholar 

  5. Kutukculer N, Moratto D, Aydinok Y, Lougaris V, Aksoylar S, Plebani A et al. Disseminated cryptosporidium infection in an infant with hyper-IgM sindrome caused by CD40 deficiency. J Pediatr 2003; 142: 194–196.

    Article  Google Scholar 

  6. Gennery AR, Khawaja K, Veys P, Bredius RG, Notarangelo LD, Mazzolari E et al. Treatment of CD40 ligand deficiency by hematopoietic stem cell transplantation: a survey of the European experience, 1993–2002. Blood 2004; 103: 1152–1157.

    Article  CAS  Google Scholar 

  7. 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: 141–142.

    Article  Google Scholar 

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Acknowledgements

This work was partially supported by European Union (EURO-POLICY-PID) grant to LDN.

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Authors and Affiliations

  1. Department of Pediatrics and ‘Angelo Nocivelli’ Institute for Molecular Medicine, University of Brescia, Brescia, Italy

    E Mazzolari, G Lanzi, C Forino, A Lanfranchi, S Giliani & L D Notarangelo

  2. Division of Pediatric Immunology, Department of Pediatrics, Faculty of Medicine, Ege University, Bornova-Izmir, Turkey

    G Aksu, C Ozturk & N Kutukculer

  3. Division of Immunology, Department of Medicine, Children's Hospital, Harvard Medical School, Boston, MA, USA

    L D Notarangelo

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  1. E Mazzolari
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  2. G Lanzi
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  3. C Forino
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  4. A Lanfranchi
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  5. G Aksu
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  6. C Ozturk
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  7. S Giliani
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  8. L D Notarangelo
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  9. N Kutukculer
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Correspondence to L D Notarangelo.

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Mazzolari, E., Lanzi, G., Forino, C. et al. First report of successful stem cell transplantation in a child with CD40 deficiency. Bone Marrow Transplant 40, 279–281 (2007). https://doi.org/10.1038/sj.bmt.1705713

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