Case Report : X-Linked SASH3 Deficiency Presenting as a Common Variable Immunodeficiency
Labrador Horrillo, Moises (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Franco-Jarava, Clara (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Garcia-Prat, Marina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Parra-Martínez, Alba (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Antolín, María (Hospital Universitari Vall d'Hebron)
Salgado-Perandrés, Sandra (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Aguiló-Cucurull, Aina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Martínez Gallo, Mónica (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Colobrán Oriol, Roger (Hospital Universitari Vall d'Hebron)
Universitat Autònoma de Barcelona

Data:	2022
Resum:	SASH3 is a lymphoid-specific adaptor protein. In a recent study, SASH3 deficiency was described as a novel X-linked combined immunodeficiency with immune dysregulation, associated with impaired TCR signaling and thymocyte survival in humans. The small number of patients reported to date showed recurrent sinopulmonary, cutaneous and mucosal infections, and autoimmune cytopenia. Here we describe an adult patient previously diagnosed with common variable immunodeficiency (CVID) due to low IgG and IgM levels and recurrent upper tract infections. Two separate, severe viral infections drew our attention and pointed to an underlying T cell defect: severe varicella zoster virus (VZV) infection at the age of 4 years and bilateral pneumonia due type A influenza infection at the age of 38. Genetic testing using an NGS-based custom-targeted gene panel revealed a novel hemizygous loss-of-function variant in the SASH3 gene (c. 505C>T/p. Gln169*). The patient's immunological phenotype included marked B cell lymphopenia with reduced pre-switch and switch memory B cells, decreased CD4 + and CD8 + naïve T cells, elevated CD4 + and CD8 + T cells, and abnormal T cell activation and proliferation. The patient showed a suboptimal response to Streptococcus pneumoniae (polysaccharide) vaccine, and a normal response to Haemophilus influenzae type B (conjugate) vaccine and SARS-CoV-2 (RNA) vaccine. In summary, our patient has a combined immunodeficiency, although he presented with a phenotype resembling CVID. Two severe episodes of viral infection alerted us to a possible T-cell defect, and genetic testing led to SASH3 deficiency. Our patient displays a milder phenotype than has been reported previously in these patients, thus expanding the clinical spectrum of this recently identified inborn error of immunity.
Ajuts:	Instituto de Salud Carlos III PI17/00660 Instituto de Salud Carlos III PI20/00761
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Combined immunodeficiency ; Common variable immunodeficiency ; Genetics ; Inborn errors of immunity ; Mutation ; Primary immunodeficiencies ; SASH3 deficiency
Publicat a:	Frontiers in immunology, Vol. 13 (april 2022) , ISSN 1664-3224

DOI: 10.3389/fimmu.2022.881206
PMID: 35464398

7 p, 6.1 MB

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