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Journal of Clinical Immunology

, Volume 36, Issue 7, pp 725–732 | Cite as

Unrelated Hematopoietic Cell Transplantation in a Patient with Combined Immunodeficiency with Granulomatous Disease and Autoimmunity Secondary to RAG Deficiency

  • Tami John
  • Jolan E. Walter
  • Catherina Schuetz
  • Karin Chen
  • Roshini S. Abraham
  • Carmem Bonfim
  • Thomas G. Boyce
  • Avni Y. Joshi
  • Elizabeth Kang
  • Beatriz Tavares Costa Carvalho
  • Arash Mahajerin
  • Diane Nugent
  • Geetha Puthenveetil
  • Amit Soni
  • Helen Su
  • Morton J. Cowan
  • Luigi Notarangelo
  • David Buchbinder
Original Article

Abstract

The use of HLA-identical hematopoietic stem cell transplantation (HSCT) demonstrates overall survival rates greater than 75 % for T-B-NK+ severe combined immunodeficiency secondary to pathogenic mutation of recombinase activating genes 1 and 2 (RAG1/2). Limited data exist regarding the use of HSCT in patients with hypomorphic RAG variants marked by greater preservation of RAG activity and associated phenotypes such as granulomatous disease in combination with autoimmunity. We describe a 17-year-old with combined immunodeficiency and immune dysregulation characterized by granulomatous lung disease and autoimmunity secondary to compound heterozygous RAG mutations. A myeloablative reduced toxicity HSCT was completed using an unrelated bone marrow donor. With the increasing cases of immune dysregulation being discovered with hypomorphic RAG variants, the use of HSCT may advance to the forefront of treatment. This case serves to discuss indications of HSCT, approaches to preparative therapy, and the potential complications in this growing cohort of patients with immune dysregulation and RAG deficiency.

Keywords

RAG deficiency primary immunodeficiency immune dysregulation autoimmunity bone marrow transplantation 

Notes

Compliance with Ethical Standards

Written consent was obtained from the patient for participation in an NIAID IRB-approved research protocol. Written consent was obtained from the patient for participation in CHOC Children’s Hospital IRB-approved research protocols.

Conflict of Interest

The authors declare that they have no competing interests.

Funding

This work was supported in part by funds from the Intramural Research Program of the National Institute of Allergy and Infectious Disease (NIAID), National Institute of Health (NIH).

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Tami John
    • 1
  • Jolan E. Walter
    • 2
  • Catherina Schuetz
    • 3
  • Karin Chen
    • 4
  • Roshini S. Abraham
    • 5
  • Carmem Bonfim
    • 6
  • Thomas G. Boyce
    • 7
  • Avni Y. Joshi
    • 5
  • Elizabeth Kang
    • 8
  • Beatriz Tavares Costa Carvalho
    • 9
  • Arash Mahajerin
    • 10
  • Diane Nugent
    • 10
  • Geetha Puthenveetil
    • 10
  • Amit Soni
    • 10
  • Helen Su
    • 8
  • Morton J. Cowan
    • 11
  • Luigi Notarangelo
    • 12
  • David Buchbinder
    • 10
  1. 1.Division of Hematology/OncologyCHOC Children’s HospitalOrangeUSA
  2. 2.Division of ImmunologyMassGeneral Hospital for ChildrenBostonUSA
  3. 3.Department of Pediatrics and Adolescent MedicineUniversity Medical Center UlmUlmGermany
  4. 4.Division of Allergy, Immunology and Rheumatology, Department of PediatricsUniversity of Utah School of MedicineSalt Lake CityUSA
  5. 5.Allergy and ImmunologyMayo ClinicRochesterUSA
  6. 6.Bone Marrow Transplantation UnitFederal University of ParanáCuritibaBrazil
  7. 7.Department of PediatricsVanderbilt University School of MedicineNashvilleUSA
  8. 8.NIAIDNational Institutes of HealthBethesdaUSA
  9. 9.Disciplina de AlergiaImunologia Clínica e Reumatologia – UNIFESPSao PauloBrazil
  10. 10.Division of HematologyCHOC Children’s HospitalOrangeUSA
  11. 11.Department of PediatricsUniversity of California, San FranciscoSan FranciscoUSA
  12. 12.Division of ImmunologyChildren’s Hospital BostonBostonUSA

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