HLH susceptibility: genetic lesions add up

Meeths, Marie; Bryceson, Yenan T.

doi:10.1182/blood-2016-03-700609

Cited by 4 publications

(3 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They also found that polygenic defects in the cytotoxic pathway led to synergistic function effects on granule-mediated lymphocyte cytotoxicity, which contributed to the development of HLH [27] . Furthermore, Sepulveda also elegantly showed that accumulation of genetic lesions might increase the likelihood of developing of HLH manifestations and cancers [28,29] . The significance of genetic mutations could not be simply considered as diagnosis evidence due to the complex factors involved in disease.…”

Section: Discussionmentioning

confidence: 99%

“…Mutations were also detected in 46.42% ENKTL cases and 27.09% ANKL cases, most of which represented monoallelic and missense. Interestingly, several previous studies had revealed a potential relationship between genetic lesions in lymphocyte cytotoxicity and cancer predisposition [28,[30][31][32] . Löfstedt et al found that heterozygous mutations in HLHcausing genes might be a risk factor for cancer.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Inherited Genetic Susceptibility to Nonimmunosuppressed Epstein-Barr Virus-associated T/NK-cell Lymphoproliferative Diseases in Chinese Patients

et al. 2021

View full text Add to dashboard Cite

SummaryEpstein-Barr virus (EBV) T/NK-cell lymphoproliferative diseases are characterized by clonal expansion of EBV-infected T or NK cells, including chronic active EBV infection of T/NK-cell type (CAEBV+T/NK), EBV-associated hemophagocytic lymphohistiocytosis (EBV+HLH), extranodal NK/T-cell lymphoma of nasal type (ENKTL), and aggressive NK-cell leukemia (ANKL). However, the role of inherited genetic variants to EBV+T/NK-LPDs susceptibility is still unknown. A total of 171 nonimmunosuppressed patients with EBV+T/NK-LPDs and 104 healthy donors were retrospectively collected and a targeted sequencing study covering 15 genes associated with lymphocyte cytotoxicity was performed. The 94 gene variants, mostly located in UNC13D, LYST, ITK, and PRF1 genes were detected, and mutations covered 28/50 (56.00%) of CAEBV-T/NK, 31/51 (60.78%) of EBV+HLH, 13/28 (46.42%) of ENKTL, and 13/48 (27.09%) of ANKL. Most mutations represented monoallelic and missense. Three-year overall survival rate of patients with CAEBV-T/NK and EBV+HLH was significantly lower in patients with germline mutations than in those without germline mutations (P=0.0284, P=0.0137). Our study provided novel insights into understanding a spectrum of nonimmunosuppressed EBV+T/NK-LPDs with respect to genetic defects associated with lymphocyte cytotoxicity and reminded us that the gene sequencing may be an auxiliary test for diagnosis and risk stratification of EBV+T/NK-LPDs.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inherited Genetic Susceptibility to Nonimmunosuppressed Epstein-Barr Virus-associated T/NK-cell Lymphoproliferative Diseases in Chinese Patients

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Homozygotes with missense, rather than nonsense, mutations present later. Heterozygote patients appear to have a lower risk of developing the disease, but likely have a higher risk than that of the general population [6]. Other patients have a polygenic tendency to hyperinflammation, and under certain circumstances, such as infection, will go on to develop sHLH.…”

Section: What Is Haemophagocytic Lymphohisticytosis (Hlh) and Who Ismentioning

confidence: 99%

Haemophagocytic lymphohisticytosis—an underrecognized hyperinflammatory syndrome

2019

View full text Add to dashboard Cite

Haemophagocytic lymphohisticytosis (HLH) is a syndrome of uncontrolled, severe systemic inflammation (hyperinflammation) arising either from a genetic immune system defect [primary (pHLH)] or triggered as a complication of malignancy, infection, or rheumatologic disease [secondary (sHLH)]. Patients with HLH often have non-specific symptoms and become progressively and critically unwell, with fever, cytopenia and multi-organ failure. Untreated, HLH is almost universally fatal, but even when treated, mortality is high, particularly when HLH complicates malignancy. HLH is managed with immunosuppression, and this can seem difficult to justify in such unwell patients. This review aims to examine the diagnostic and treatment challenges posed by sHLH and to improve recognition among rheumatologists who, being expert in the management of multisystem diseases and in the use of immunosuppression, are ideally placed to deliver care and build an evidence base for better disease characterization and treatment.

show abstract