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From Severe Combined Immunodeficiency to Omenn syndrome after hematopoietic stem cell transplantation in a RAG1 deficient family

Authors

  • Laura Martinez-Martinez,

    1. Immunology, Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Pare Claret, Barcelona, Spain
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    • Equally contributed as first authors.

  • Marta Vazquez-Ortiz,

    1. Pediatric Allergy and Clinical Immunology Department, Hospital Sant Joan de Deu, Universitat de Barcelona, Passeig de Sant Joan de Deu, Spain
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    • Equally contributed as first authors.

  • Cecilia Gonzalez-Santesteban,

    1. Immunology, Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Pare Claret, Barcelona, Spain
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  • Andrea Martin-Nalda,

    1. Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebrón, Passeig de la Vall d’Hebrón, Barcelona, Spain
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  • Asunción Vicente,

    1. Pediatric Dermatology, Hospital Sant Joan de Deu, Universitat de Barcelona, Passeig de Sant Joan de Deu, Spain
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  • Ana M. Plaza,

    1. Pediatric Allergy and Clinical Immunology Department, Hospital Sant Joan de Deu, Universitat de Barcelona, Passeig de Sant Joan de Deu, Spain
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  • Isabel Badell,

    1. Pediatrics, Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Pare Claret, Barcelona, Spain
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  • Laia Alsina,

    1. Pediatric Allergy and Clinical Immunology Department, Hospital Sant Joan de Deu, Universitat de Barcelona, Passeig de Sant Joan de Deu, Spain
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  • Oscar de la Calle-Martin

    1. Immunology, Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Pare Claret, Barcelona, Spain
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Oscar de la Calle-Martin, Immunology, Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, C/Pare Claret, 167, E08025 Barcelona, Spain.
Tel.: +34 93 553 7265
Fax: +34 93 553 7598
E-mail: odlcalle@santpau.cat
Laia Alsina, Pediatric Allergy and Clinical Immunology, Hospital Sant Joan de Deu, Universitat de Barcelona, Passeig de Sant Joan de Deu, 2, E08950 Spain.
Tel.: +34 93 280 4000, ext. 3330
Fax: +34 93 203 3959
E-mail: lalsina@hsjdbcn.org

Abstract

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.

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