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Clinical, Immunological, and Molecular Characterization of Hyper-IgM Syndrome Due to CD40 Deficiency in Eleven Patients

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Abstract

Purpose

Hyper-IgM syndrome due to CD40 deficiency (HIGM3) is a rare form of primary immunodeficiency with few reported cases. In this study, we further characterize the clinical, immunological, and molecular profiles of the disease in a cohort of 11 patients.

Methods

Molecular genetic analysis and a comprehensive clinical review of patients diagnosed with HIGM3 at our tertiary care center from 1994 to 2011 were undertaken.

Results

Eleven patients from seven families were enrolled. The patients had a median age of 9 years [ranging from 2 to 22 years old]. All 11 patients had recurrent chest infections at presentation. Pneumocystis jiroveci pneumonia was confirmed in three patients. Five patients had sclerosing cholangitis, and five patients had Cryptosporidium isolated from their stool. Six patients had nasal and sinus infections, and two of these patients had destructive nasal fungal infections. Eight patients had neutropenia. All of the patients had low IgG and normal or high IgM levels. IgA was undetectable in all but three patients. Two novel mutations were found: a splice site for intron 3 and a missense mutation located in the coding region of exon 3. Two patients underwent successful stem cell transplantation from a matched donor. Four patients are doing well on prophylaxis; two are very sick, one with protracted diarrhea and persistent Cryptosporidium and the other with neurological complications. Three patients died early in life as a result of severe sepsis.

Conclusions

To our knowledge, this report provides the largest cohort of patients with this disease with a very long follow-up period. Our cohort showed variable disease severity.

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Acknowledgments

We would like to thank the following individuals: Dr. Abdelmoneim Eldali for help with the statistical analysis; Dr. Sriharsha Kantamnini for his advice on technical issues related to Western blot analysis; Dr. Entissar Al-Suhaibani for her support of the MSc student, Hanadi Al- Asseri, one of the authors of this manuscript; and the Flow Cytometry section staff (Ameena Siefeldien, Margarida Gillbee and Shar Al-Janadi).

Funding

King Faisal Specialist Hospital and Research Centre

Author information

Authors and Affiliations

  1. Section of Allergy and Immunology, Department of Pediatrics, MBC-58, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh, 11211, Saudi Arabia

    Bandar K. Al-Saud, Zobaida Al-Sum, Abdulaziz Al-Ghonaium, Saleh Al-Muhsen, Hasan Al-Dhekri, Rand Arnaout & Hamoud Al-Mousa

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

    Bandar K. Al-Saud, Rand Arnaout & Hamoud Al-Mousa

  3. Genetics Department, Research Centre, MBC-03, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh, 11211, Saudi Arabia

    Hanadi Alassiri, Osama Alsmadi, Esteban Borrero, Asm’a Abu-Staiteh & Abbas Hawwari

  4. King Saud University, Riyadh, Saudi Arabia

    Hanadi Alassiri & Saleh Al-Muhsen

  5. Pathology & Laboratory Medicine Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

    Faisal Rawas

Authors
  1. Bandar K. Al-Saud
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  2. Zobaida Al-Sum
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  3. Hanadi Alassiri
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  4. Abdulaziz Al-Ghonaium
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  7. Rand Arnaout
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  10. Asm’a Abu-Staiteh
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  11. Faisal Rawas
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  12. Hamoud Al-Mousa
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Corresponding authors

Correspondence to Bandar K. Al-Saud or Abbas Hawwari.

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Al-Saud, B.K., Al-Sum, Z., Alassiri, H. et al. Clinical, Immunological, and Molecular Characterization of Hyper-IgM Syndrome Due to CD40 Deficiency in Eleven Patients. J Clin Immunol 33, 1325–1335 (2013). https://doi.org/10.1007/s10875-013-9951-9

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  • DOI: https://doi.org/10.1007/s10875-013-9951-9

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