From Severe Combined Immunodeficiency to Omenn syndrome after hematopoietic stem cell transplantation in a RAG1 deficient family
Por:
Martinez-Martinez, L, Vazquez-Ortiz, M, Gonzalez-Santesteban, C, Martin-Nalda, A, Vicente, A, Plaza, AM, Badell, I, Alsina, L, de la Calle-Martin, O
Publicada:
1 nov 2012
Resumen:
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 patients 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 patients outcome and it should be considered in similar cases.
Filiaciones:
Martinez-Martinez, L:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, E-08025 Barcelona, Spain
Vazquez-Ortiz, M:
Univ Barcelona, Hosp St Joan de Deu, Pediat Allergy & Clin Immunol Dept, E-08950 Passeig De St Joan Deu, Spain
Gonzalez-Santesteban, C:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, E-08025 Barcelona, Spain
Martin-Nalda, A:
Hosp Univ Vall DHebron, Pediat Infect Dis & Immunodeficiencies Unit, Barcelona, Spain
Plaza, AM:
Univ Barcelona, Hosp St Joan de Deu, Pediat Allergy & Clin Immunol Dept, E-08950 Passeig De St Joan Deu, Spain
Badell, I:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, E-08025 Barcelona, Spain
Alsina, L:
Univ Barcelona, Hosp St Joan de Deu, Pediat Allergy & Clin Immunol Dept, E-08950 Passeig De St Joan Deu, Spain
de la Calle-Martin, O:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, E-08025 Barcelona, Spain
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