Equally contributed as first authors.
From Severe Combined Immunodeficiency to Omenn syndrome after hematopoietic stem cell transplantation in a RAG1 deficient family
Article first published online: 13 AUG 2012
© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd
Pediatric Allergy and Immunology
Volume 23, Issue 7, pages 660–666, November 2012
How to Cite
Martinez-Martinez, L., Vazquez-Ortiz, M., Gonzalez-Santesteban, C., Martin-Nalda, A., Vicente, A., Plaza, A. M., Badell, I., Alsina, L. and de la Calle-Martin, O. (2012), From Severe Combined Immunodeficiency to Omenn syndrome after hematopoietic stem cell transplantation in a RAG1 deficient family. Pediatric Allergy and Immunology, 23: 660–666. doi: 10.1111/j.1399-3038.2012.01339.x
- Issue published online: 29 OCT 2012
- Article first published online: 13 AUG 2012
- Accepted for publication 9 June 2012
- atypical Severe Combined Immunodeficiency/Omenn syndrome;
- autoreactive T cells;
- hematopoietic stem cell transplantation;
- Omenn syndrome;
- RAG genes;
- Severe Combined Immunodeficiency
Background: Mutations in RAG genes cause a spectrum of severe immunodeficiencies ranging from Severe Combined Immunodeficiency (SCID) T-B-NK+ to Omenn syndrome (OS) through intermediate phenotypes, even for the same alteration. Nowadays, hematopoietic stem cell transplantation (HSCT) is the unique curative treatment available.
Methods: We describe three related patients from a Moroccan consanguineous family. Patient 1 developed at 1 month of age moderate eczematous dermatitis with eosinophilia, followed by infections and enteritis. He was transplanted and received reduced intensity conditioning regimen previous to HSCT. His brother, patient 2, was born preterm with a severe neonatal erythroderma, hepatosplenomegaly and lymphadenopathy. Patient 3, cousin of the two siblings, was also born preterm and fulfilled all criteria for classical OS. Immunological evaluation was performed and RAG genes were sequenced.
Results: Immunological data from all three patients were very diversed, from T lymphopenia to marked lymphocytosis, and different degrees of eosinophilia and IgE levels. Non-responder T cells and absent B cells were constant. All patients presented the same homozygous mutation in RAG1 gene (c.631delT). Patient 1 fully recovered both clinically and immunologically after HSCT. Two years later, he lost the accomplished lymphoid chimera and the disease relapsed as a classical OS, leading to patient’s death.
Conclusions: This is the first report of a RAG1 deficient patient with a changed clinical and immunological phenotype from SCID to OS after HSCT. The use of a myeloablative conditioning regimen that eliminates reminiscent T cells might have improved patient’s outcome and it should be considered in similar cases.