Novel MALT1 Mutation Linked to Immunodeficiency, Immune Dysregulation, and an Abnormal T Cell Receptor Repertoire.
J Clin Immunol
; 39(4): 401-413, 2019 05.
Article
em En
| MEDLINE
| ID: mdl-31037583
ABSTRACT
MALT1 (mucosa-associated lymphoid tissue lymphoma-translocation gene 1) is an intracellular signaling protein that activates NFκB and is crucial for both the adaptive and innate immune responses. Only 6 patients with immune deficiencies secondary to inherited mutations in the MALT1 gene have been described. PURPOSE:
To provide clinical and immunological insights from 2 patients diagnosed with MALT1 immunodeficiency syndrome due to a novel MALT1 mutation.METHODS:
Two cousins with suspected combined immunodeficiency underwent immunological and genetic work-up, including lymphocyte phenotyping, lymphocyte activation by mitogen stimulation, and next-generation sequencing (NGS) of T cell receptor gamma chain (TRG) repertoire. Whole exome sequencing was performed to identify the underlying genetic defect.RESULTS:
Clinical findings included recurrent infections, failure to thrive, lymphadenopathy, dermatitis, and autoimmunity. Immune work-up revealed lymphocytosis, low to normal levels of immunoglobulins, absence of regulatory T cells, and low Th17 cells. A normal proliferative response was induced by phytohemagglutinin and IL-2 but was diminished with anti-CD3. TRG repertoire was diverse with a clonal expansion pattern. Genetic analysis identified a novel autosomal recessive homozygous c.1799T>A; p. I600N missense mutation in MALT1. MALT1 protein expression was markedly reduced, and in vitro IL-2 production and NFκB signaling pathway were significantly impaired.CONCLUSIONS:
Two patients harboring a novel MALT1 mutation presented with signs of immune deficiency and dysregulation and were found to have an abnormal T cell receptor repertoire. These findings reinforce the link between MALT1 deficiency and combined immunodeficiency. Early diagnosis is crucial, and curative treatment by hematopoietic stem cell transplantation may be warranted.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos T
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Predisposição Genética para Doença
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Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa
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Síndromes de Imunodeficiência
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Mutação
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
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Screening_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
J Clin Immunol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Israel