Makale detayı · 2007
Defective cytotoxic lymphocyte degranulation in syntaxin 11 deficient familial hemophagocytic lymphohistiocytosis 4 FHL4 patients
- Yıl
- 2007
- Tür
- article
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- YÖKSİS dergi adı Blood
- Katalog eşleşmesi (ISSN) Blood
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Özet
OpenAlex · İngilizce
Familial hemophagocytic lymphohistiocytosis (FHL) is typically an early onset, fatal disease characterized by a sepsislike illness with cytopenia, hepatosplenomegaly, and deficient lymphocyte cytotoxicity. Disease-causing mutations have been identified in genes encoding perforin (PRF1/FHL2), Munc13-4 (UNC13D/FHL3), and syntaxin-11 (STX11/FHL4). In contrast to mutations leading to loss of perforin and Munc13-4 function, it is unclear how syntaxin-11 loss-of-function mutations contribute to disease. We show here that freshly isolated, resting natural killer (NK) cells and CD8(+) T cells express syntaxin-11. In infants, NK cells are the predominant perforin-containing cell type. NK cells from FHL4 patients fail to degranulate when encountering susceptible target cells. Unexpectedly, IL-2 stimulation partially restores degranulation and cytotoxicity by NK cells, which could explain the less severe disease progression observed in FHL4 patients, compared with FHL2 and FHL3 patients. Since the effector T-cell compartment is still immature in infants, our data suggest that the observed defect in NK-cell degranulation may contribute to the pathophysiology of FHL, that evaluation of NK-cell degranulation in suspected FHL patients may facilitate diagnosis, and that these new insights may offer novel therapeutic possibilities.
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Yerel katalogda bu makaleye atıf yapan 15 yayın (OpenAlex referans eşleşmesi; tam dünya listesi değildir).
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- Structural and functional analysis of perforin mutations in associationwith clinical data of familial hemophagocytic lymphohistiocytosis type 2 FHL2 patients 2013
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- Hemophagocytic syndrome in a 4 month old infant with biotinidase deficiency 2012