Clinical Phenotypes and Immunological Characteristics of 18 Egyptian LRBA Deficiency Patients.
J Clin Immunol
; 40(6): 820-832, 2020 08.
Article
en En
| MEDLINE
| ID: mdl-32506362
ABSTRACT
LPS-responsive beige-like anchor (LRBA) deficiency is an autosomal recessive primary immunodeficiency disorder, OMIM (#614700). LRBA deficiency patients suffer from variable manifestations including recurrent infections, immune dysregulation, autoimmunity, cytopenias, and enteropathy. This study describes different clinical phenotypes and immunological characteristics of 18 LRBA deficiency patients diagnosed from Egypt. T and B lymphocyte subpopulations, LRBA, and cytotoxic T lymphocyte-associated protein 4 (CTLA4) expression were evaluated in resting and stimulated T cells using flow cytometry. Next-generation sequencing was used to identify mutations in the LRBA gene. LRBA deficiency patients had significantly lower B cells and increased percentage of memory T cells. CTLA4 levels were lower in LRBA-deficient T regulatory cells in comparison to healthy donors at resting conditions and significantly increased upon stimulation of T cells. We identified 11 novel mutations in LRBA gene ranging from large deletions to point mutations. Finally, we were able to differentiate LRBA-deficient patients from healthy control and common variable immunodeficiency patients using a simple flow cytometry test performed on whole blood and without need to prior stimulation. LRBA deficiency has heterogeneous phenotypes with poor phenotype-genotype correlation since the same mutation may manifest differently even within the same family. Low LRBA expression, low numbers of B cells, increased numbers of memory T cells, and defective CTLA4 expression (which increase to normal level upon T cell stimulation) are useful laboratory tests to establish the diagnosis of LRBA deficiency. Screening of the siblings of affected patients is very important as patients may be asymptomatic at the beginning of the disease course.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Fenotipo
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Predisposición Genética a la Enfermedad
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Proteínas Adaptadoras Transductoras de Señales
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Estudios de Asociación Genética
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Síndromes de Inmunodeficiencia
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Child
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Child, preschool
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Female
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Humans
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Infant
/
Male
País/Región como asunto:
Africa
Idioma:
En
Revista:
J Clin Immunol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Egipto