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Case Report: X-Linked SASH3 Deficiency Presenting as a Common Variable Immunodeficiency.
Labrador-Horrillo, Moisés; Franco-Jarava, Clara; Garcia-Prat, Marina; Parra-Martínez, Alba; Antolín, María; Salgado-Perandrés, Sandra; Aguiló-Cucurull, Aina; Martinez-Gallo, Mónica; Colobran, Roger.
  • Labrador-Horrillo M; Allergy Section, Internal Medicine Department, Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Research Institute (VHIR) RETIC ARADyal, Vall d'Hebron Barcelona Hospital, Autonomous University of Barcelona (UAB), Barcelona, Spain.
  • Franco-Jarava C; Immunology Division, Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Barcelona Hospital, Barcelona, Spain.
  • Garcia-Prat M; Translational Immunology Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital, Barcelona, Spain.
  • Parra-Martínez A; Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona (UAB), Bellaterra, Spain.
  • Antolín M; Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Spain.
  • Salgado-Perandrés S; Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Spain.
  • Aguiló-Cucurull A; Pediatric Infectious Diseases and Immunodeficiencies Unit, Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Barcelona Hospital, Barcelona, Spain.
  • Martinez-Gallo M; Infection in Immunocompromised Pediatric Patients Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital, Barcelona, Spain.
  • Colobran R; Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Spain.
Front Immunol ; 13: 881206, 2022.
Article in English | MEDLINE | ID: covidwho-1809410
ABSTRACT
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+ TEMRA 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Vaccines / Common Variable Immunodeficiency / Primary Immunodeficiency Diseases / COVID-19 Type of study: Case report / Diagnostic study / Prognostic study Topics: Long Covid / Vaccines / Variants Limits: Humans / Male Language: English Journal: Front Immunol Year: 2022 Document Type: Article Affiliation country: Fimmu.2022.881206

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Vaccines / Common Variable Immunodeficiency / Primary Immunodeficiency Diseases / COVID-19 Type of study: Case report / Diagnostic study / Prognostic study Topics: Long Covid / Vaccines / Variants Limits: Humans / Male Language: English Journal: Front Immunol Year: 2022 Document Type: Article Affiliation country: Fimmu.2022.881206