STX11‐deficient familial hemophagocytic lymphohistiocytosis type 4 is associated with self‐resolving flares and a milder clinical course

Kram, David E.; Santarelli, Michael D.; Russell, Thomas B.; Pearsall, Katharine; Saldaña, Blachy J. Dávila

doi:10.1002/pbc.27890

Cited by 5 publications

(4 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…43 As STX11 plays a nonredundant role in platelet secretion, FHL4 patients may present with defective platelet secretion and bleeding history. 44 Although STX11 and STXB2 act as partners at the IS, patients with FHL4 seem to have milder phenotype 45 ; moreover, gastrointestinal symptoms may be observed in FHL5 as Munc18-2 is expressed also in intestinal epithelium and defective neutrophils granules may result in inadequate bacteria-gut clearance. 46,47 Within IEI with hypopigmentation, the transient or chronic neutropenia seen in CHS and GS2 or HPS2, respectively, is the consequence of the impair distribution of secretory giant lysosomes of phagocytes that impairs neutrophil chemotaxis.…”

Section: Pathophysiologymentioning

confidence: 99%

“…As STX11 plays a nonredundant role in platelet secretion, FHL4 patients may present with defective platelet secretion and bleeding history 44 . Although STX11 and STXB2 act as partners at the IS, patients with FHL4 seem to have milder phenotype 45 ; moreover, gastrointestinal symptoms may be observed in FHL5 as Munc18‐2 is expressed also in intestinal epithelium and defective neutrophils granules may result in inadequate bacteria‐gut clearance 46,47 …”

Section: Review Of the Literaturementioning

confidence: 99%

See 1 more Smart Citation

Pediatric inborn errors of immunity causing hemophagocytic lymphohistiocytosis: Case report and review of the literature

Caldirola

Raccio

Giovanni

et al. 2022

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Inborn errors of immunity are a group of genetic disorders caused by mutations that affect the development and/or function of several compartments of the immune system, predisposing patients to infections, autoimmunity, allergy and malignancies. In this regard, mutations that affect proteins involved in trafficking, priming, docking, or membrane fusion will impair the exocytosis of lytic granules of effector NK and cytotoxic T lymphocytes. This may predispose patients to hemophagocytic lymphohistiocytosis, a life‐threatening immune disorder characterized by systemic lymphocyte and macrophage activation, and increased levels of cytokines, which lead to an uncontrolled hyperinflammation state and progressive multiorgan damage. In this review, we will describe a clinical case and recent advances in inborn errors of immunity predisposing to hemophagocytic lymphohistiocytosis. Summary sentence: Review of recent advances in inborn errors of immunity predisposing to hemophagocytic lymphohistiocytosis.

show abstract

Section: Pathophysiologymentioning

confidence: 99%

Section: Review Of the Literaturementioning

confidence: 99%

Pediatric inborn errors of immunity causing hemophagocytic lymphohistiocytosis: Case report and review of the literature

Caldirola

Raccio

Giovanni

et al. 2022

Journal of Leukocyte Biology

View full text Add to dashboard Cite

show abstract

Section: Snares and Developmental Disorders Of The Immune Systemmentioning

confidence: 99%

“…Different types of STX11 mutations that are associated with FHL4 have been identified (X. Guo et al, 2019; Kram et al, 2019; Rudd et al, 2006; zur Stadt et al, 2005). FHL4 resulting from STX11 mutations is typically late‐onset and often with milder symptoms compared to the perforin‐deficient FLH2 subtypes (Kram et al, 2019; Sepulveda et al, 2013), and even a case with homozygous nonsense mutations are relatively treatment responsive (X. Guo et al, 2019). Comparison between STX11‐deficient and perforin‐deficient mice that developed HLH when challenged with lymphocytic choriomeningitis virus indicated that HLH progression is not fatal for the former due to T cell exhaustion (Kögl et al, 2013).…”

Section: Snares and Developmental Disorders Of The Immune Systemmentioning

confidence: 99%

SNAREs and developmental disorders

Tang

2020

Journal Cellular Physiology

View full text Add to dashboard Cite

Members of the soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE) family mediate membrane fusion processes associated with vesicular trafficking and autophagy. SNAREs mediate core membrane fusion processes essential for all cells, but some SNAREs serve cell/tissue type‐specific exocytic/endocytic functions, and are therefore critical for various aspects of embryonic development. Mutations or variants of their encoding genes could give rise to developmental disorders, such as those affecting the nervous system and immune system in humans. Mutations to components in the canonical synaptic vesicle fusion SNARE complex (VAMP2, STX1A/B, and SNAP25) and a key regulator of SNARE complex formation MUNC18‐1, produce variant phenotypes of autism, intellectual disability, movement disorders, and epilepsy. STX11 and MUNC18‐2 mutations underlie 2 subtypes of familial hemophagocytic lymphohistiocytosis. STX3 mutations contribute to variant microvillus inclusion disease. Chromosomal microdeletions involving STX16 play a role in pseudohypoparathyroidism type IB associated with abnormal imprinting of the GNAS complex locus. In this short review, I discuss these and other SNARE gene mutations and variants that are known to be associated with a variety developmental disorders, with a focus on their underlying cellular and molecular pathological basis deciphered through disease modeling. Possible pathogenic potentials of other SNAREs whose variants could be disease predisposing are also speculated upon.

show abstract

STX11 Deficiency

Chinn

2020

Encyclopedia of Medical Immunology

View full text Add to dashboard Cite

STX11‐deficient familial hemophagocytic lymphohistiocytosis type 4 is associated with self‐resolving flares and a milder clinical course

Cited by 5 publications

References 15 publications

Pediatric inborn errors of immunity causing hemophagocytic lymphohistiocytosis: Case report and review of the literature

Pediatric inborn errors of immunity causing hemophagocytic lymphohistiocytosis: Case report and review of the literature

SNAREs and developmental disorders

STX11 Deficiency

Contact Info

Product

Resources

About