Case Report: X-Linked SASH3 Deficiency Presenting as a Common Variable Immunodeficiency.
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.
Keywords
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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