A boy with X-linked hyper-IgM syndrome and natural killer cell deficiency

Østenstad, Bjørn; Giliani, Silvia; Oj, Mellbye; Nilsen, B.; Tg, Abrahamsen

doi:10.1111/j.1365-2249.1997.284-ce1174.x

Cited by 18 publications

(8 citation statements)

References 23 publications

(37 reference statements)

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“…NK cells of TNF-or LT-a-deficient mice have defective abilities to reject tumors [12] and to eliminate metastases [13]. In addition, patients with mutation of the CD40L gene and failure to express the functional ligand on activated T cells (X-linked hyper-IgM syndrome) develop cholangiopathy and multiple malignancies in the pancreas, liver, and biliary tree [14] as well as NK cell deficiency [15]. Therefore, mutation-caused functional defects of TNFSFL and their receptors may contribute to the pathogenesis and progression of tumors.…”

Section: Tnfsfl Mediate Anticancer Activitymentioning

confidence: 99%

Role of TNF superfamily ligands in innate immunity

Vujanović

2011

Immunol Res

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Natural killer (NK) cells and dendritic cells (DCs) are essential effector cells of the innate immune system that rapidly recognize and eliminate microbial pathogens and abnormal cells, and induce and regulate adaptive immune functions. While NK cells express perforin and granzymes in the lysosomal granules and transmembrane tumor necrosis factor superfamily ligands (tmTNFSFL) on the plasma membrane, DCs express only tmTNFSFL on the plasma membrane. Perforin and granzymes are cytolytic molecules, which NK cells use to mediate a secretory/necrotic killing mechanism against rare leukemia cell targets. TNFSFL are pleiotropic transmembrane molecules, which can mediate a variety of important functions such as apoptosis, development of peripheral lymphoid tissues, inflammation and regulation of immune functions. Using tmTNFSFL, NK cells and DCs mediate a cell contact-dependent non-secretory apoptotic cytotoxic mechanism against virtually all types of cancer cells, and cross talk that leads to polarization and reciprocal stimulation and amplification of Th1 type cytokines secreted by NK cells and DCs. In this paper, we review and discuss the supporting evidence of the non-secretory, tmTNFSFL-mediated innate mechanisms of NK cells and DCs, their roles in anticancer immune defense and potential of their modulation and use in prevention and treatment of cancer.

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Section: Tnfsfl Mediate Anticancer Activitymentioning

confidence: 99%

Role of TNF superfamily ligands in innate immunity

Vujanović

2011

Immunol Res

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“…Their function in host defense in humans remains unclear, due to the lack of well-defined inherited disorders associated with a selective defect in NK cell development (7). Several children with a specific quantitative circulating NK cell defect but normal T cell counts have been reported (8)(9)(10)(11)(12). Some of these patients seem to be highly susceptible to viral infections, such as those caused by herpesviruses, in particular (8,9).…”

Section: Introductionmentioning

confidence: 99%

Partial MCM4 deficiency in patients with growth retardation, adrenal insufficiency, and natural killer cell deficiency

Gineau¹,

Cognet²,

Kara³

et al. 2012

J. Clin. Invest.

273

286

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Natural killer (NK) cells are circulating cytotoxic lymphocytes that exert potent and nonredundant antiviral activity and antitumoral activity in the mouse; however, their function in host defense in humans remains unclear. Here, we investigated 6 related patients with autosomal recessive growth retardation, adrenal insufficiency, and a selective NK cell deficiency characterized by a lack of the CD56 dim NK subset. Using linkage analysis and fine mapping, we identified the disease-causing gene, MCM4, which encodes a component of the MCM2-7 helicase complex required for DNA replication. A splice-site mutation in the patients produced a frameshift, but the mutation was hypomorphic due to the creation of two new translation initiation methionine codons downstream of the premature termination codon. The patients' fibroblasts exhibited genomic instability, which was rescued by expression of WT MCM4. These data indicate that the patients' growth retardation and adrenal insufficiency likely reflect the ubiquitous but heterogeneous impact of the MCM4 mutation in various tissues. In addition, the specific loss of the NK CD56 dim subset in patients was associated with a lower rate of NK CD56 bright cell proliferation, and the maturation of NK CD56 bright cells toward an NK CD56 dim phenotype was tightly dependent on MCM4-dependent cell division. Thus, partial MCM4 deficiency results in a genetic syndrome of growth retardation with adrenal insufficiency and selective NK deficiency.

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“…Neutropenia is observed in as many as 60% of patients according to the US registry report [26]. There have been three separate reported cases of G-CSF administration for neutropenia in HIGM, and all demonstrated an increase in ANC and a reduction in the incidence of infection [27][28][29]. One patient was also noted to have an NK cell deficiency and had an increase in NK cell number after therapy [27].…”

Section: G-csf and Gm-csfmentioning

confidence: 99%

“…There have been three separate reported cases of G-CSF administration for neutropenia in HIGM, and all demonstrated an increase in ANC and a reduction in the incidence of infection [27][28][29]. One patient was also noted to have an NK cell deficiency and had an increase in NK cell number after therapy [27]. Treatment resulted in an increase in ANC and NK cells and no further serious infections.…”

Section: G-csf and Gm-csfmentioning

confidence: 99%

Use of Cytokine Therapy in Primary Immunodeficiency

Roy-Ghanta

2009

Clinic Rev Allerg Immunol

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Of the six cytokine therapies approved by the US Food and Drug Administration, five of them have been used in patients with primary immunodeficiency (PID). In some applications, clear benefits have been demonstrated, while in others, effects have been more marginal. The most compelling current applications of cytokine therapy in PID are those of granulocyte colony stimulating factor in severe congenital neutropenia and interferon gamma in chronic granulomatous disease. Despite encouraging results with interleukin-2 in common variable immunodeficiency and select other indications, its use in PID is not widespread.

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A boy with X-linked hyper-IgM syndrome and natural killer cell deficiency

Cited by 18 publications

References 23 publications

Role of TNF superfamily ligands in innate immunity

Role of TNF superfamily ligands in innate immunity

Partial MCM4 deficiency in patients with growth retardation, adrenal insufficiency, and natural killer cell deficiency

Use of Cytokine Therapy in Primary Immunodeficiency

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