T Cell Impairment Is Predictive for a Severe Clinical Course in NEMO Deficiency.
J Clin Immunol
; 40(3): 421-434, 2020 04.
Article
em En
| MEDLINE
| ID: mdl-31965418
ABSTRACT
PURPOSE:
NEMO-deficient patients present with variable degrees of immunodeficiency. Accordingly, treatment ranges from antibiotic prophylaxis and/or IgG-substitution to allogenic hematopoietic stem cell transplantation (HSCT). The correct estimation of the immunodeficiency is essential to avoid over- as well as under-treatment. We compare the immunological phenotype of a NEMO-deficient patient with a newly-described splice site mutation that causes truncation of the NEMO zinc-finger (ZF) domain and a severe clinical course with the immunological phenotype of three NEMO-deficient patients with missense mutations and milder clinical courses and all previously published patients.METHODS:
Lymphocyte subsets, proliferation, and intracellular NEMO-expression were assessed by FACS. NF-κB signal transduction was determined by measuring IκBα-degradation and the production of cytokines upon stimulation with TNF-α, IL-1ß, and TLR-agonists in immortalized fibroblasts and whole blood, respectively.RESULTS:
The patient with truncated ZF-domain of NEMO showed low levels of IgM and IgG, reduced class-switched memory B cells, almost complete skewing towards naïve CD45RA+ T cells, impaired T cell proliferation as well as cytokine production upon stimulation with TNF-α, IL-1ß, and TLR-agonists. He suffered from severe infections (sepsis, pneumonia, osteomyelitis) during infancy. In contrast, three patients with missense mutations in IKBKG presented neither skewing of T cells towards naïvety nor impaired T cell proliferation. They are stable on prophylactic IgG-substitution or even off any prophylactic treatment.CONCLUSION:
The loss of the ZF-domain and the impaired T cell proliferation accompanied by almost complete persistence of naïve T cells despite severe infections are suggestive for a profound immunodeficiency. Allogenic HSCT should be considered early for these patients before chronic sequelae occur.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Deleção de Sequência
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Quinase I-kappa B
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Genótipo
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Síndromes de Imunodeficiência
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
J Clin Immunol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Alemanha