A novel homozygous Y140X mutation of ISG15 causes diverse type I interferonopathies in sibling patients with cutaneous lesions or recurrent parenchymal pneumonia.
Clin Immunol
; 257: 109844, 2023 12.
Article
em En
| MEDLINE
| ID: mdl-37984483
ABSTRACT
PURPOSE:
Interferon-stimulated gene 15 (ISG15) deficiency, a rare human inborn error of immunity characterized by susceptibility to Bacillus Calmette-Guerin (BCG) diseases, neuropathic and dermatological manifestations.METHODS:
The clinical and immunological features of two siblings with ISG15 deficiency combined with asymptomatic myeloperoxidase (MPO) mutations were analyzed, and their pathogenesis, as well as target therapeutic candidates, were explored.RESULTS:
The manifestation in patient 2 was skin lesions, while those in patient 1 were intracranial calcification and recurrent pneumonia. Whole-exome identified novel, dual mutations in ISG15 and MPO. PBMCs and B cell lines derived from the patients showed hyper-activated JAK/STAT signaling. Normal neutrophil function excluded pathogenicity caused by the MPO mutation. RNA sequencing identified baricitinib as therapeutic candidate.CONCLUSIONS:
We report two sibling patients harboring the same novel ISG15 mutation showing diverse clinical features, and one harbored a rare phenotype of pneumonia. These findings expand the clinical spectrum of ISG15 deficiency and identify baricitinib as therapeutic candidate.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pneumonia
/
Interferons
Limite:
Humans
Idioma:
En
Revista:
Clin Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2023
Tipo de documento:
Article