Genome-wide association study identifies susceptibility loci for dengue shock syndrome at MICB and PLCE1

Khor, Chiea‐Chuen; Chau, Tran Nguyen Bich; Pang, Junxiong; Dávila, Sonia; Long, Hoang Truong; Ong, Rick Twee‐Hee; Dunstan, Sarah J.; Wills, Bridget; Farrar, Jeremy; Tram, Ta Van; Gan, Tran Thi; Binh, Nguyen Thi Nguyet; Tri, Le Trung; Lien, Le Bich; Tuấn, Nguyễn Minh; Thắm, Nguyễn Thị; Lanh, Mai Ngoc; Nguyet, Nguyen Minh; Hieu, Nguyen Trong; Châu, Nguyễn Văn Vĩnh; Thúy, Trần Thi; Tan, Dennis Eng Kiat; Sakuntabhai, Anavaj; Teo, Yik Ying; Hibberd, Martin L.; Simmons, Cameron P.

doi:10.1038/ng.960

Cited by 189 publications

(155 citation statements)

References 32 publications

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“…Patients with focal segmental glomerulosclerosis have been found to have loss-of-function mutations in PLCe1, and PLCe1 itself interacts with transient receptor potential channel 6 (24)(25)(26)(27). Even more intriguing is the fact that a genome-wide association study identified the susceptibility loci for dengue shock syndrome at PLCe1 (28). Whether mutations in PLCe1 are directly responsible for this clinical syndrome remains unclear.…”

Section: Discussionmentioning

confidence: 99%

PLCε1 regulates SDF-1α–induced lymphocyte adhesion and migration to sites of inflammation

Strazza

Azoulay-Alfaguter

Peled

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Regulation of integrins is critical for lymphocyte adhesion to endothelium and migration throughout the body. Inside-out signaling to integrins is mediated by the small GTPase Ras-proximate-1 (Rap1). Using an RNA-mediated interference screen, we identified phospholipase Ce 1 (PLCe1) as a crucial regulator of stromal cell-derived factor 1 alpha (SDF-1α)-induced Rap1 activation. We have shown that SDF-1α-induced activation of Rap1 is transient in comparison with the sustained level following cross-linking of the antigen receptor. We identified that PLCe1 was necessary for SDF-1α-induced adhesion using shear stress, cell morphology alterations, and crawling on intercellular adhesion molecule 1 (ICAM-1)-expressing cells. Structurefunction experiments to separate the dual-enzymatic function of PLCe1 uncover necessary contributions of the CDC25, Pleckstrin homology, and Ras-associating domains, but not phospholipase activity, to this pathway. In the mouse model of delayed type hypersensitivity, we have shown an essential role for PLCe1 in T-cell migration to inflamed skin, but not for cytokine secretion and proliferation in regional lymph nodes. Our results reveal a signaling pathway where SDF-1α induces T-cell adhesion through activation of PLCe1, suggesting that PLCe1 is a specific potential target in treating conditions involving migration of T cells to inflamed organs.

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Section: Discussionmentioning

confidence: 99%

PLCε1 regulates SDF-1α–induced lymphocyte adhesion and migration to sites of inflammation

Strazza

Azoulay-Alfaguter

Peled

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…In particular, given that host, 6 viral, and possibly vector-related factors [7][8][9] influence disease outcome, cross-sectional studies that compare primary and secondary infections may be confounded by many factors other than the serologic status of dengue at the point of infection. Cohort studies could address this question, although such studies are complex and resource intensive.…”

Section: Introductionmentioning

confidence: 99%

Research on Dengue During World War II Revisited

Snow¹,

Haaland²,

Ooi³

et al. 2014

The American Society of Tropical Medicine and Hygiene

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Abstract. Much of the basic clinical information about dengue infection comes from experimental human studies conducted in the 1920s and 1940s. Albert Sabin's original laboratory records from one such study were bequeathed to Duane J. Gubler. These records were reviewed and 150 experiments were included in our analyses. Persons were inoculated with dengue virus 1 (DENV-1) and DENV-2. Median fever duration was shorter in primary DENV-2 infections compared with DENV-1, although maximum temperature and severity of illness were comparable. At 1.5-9 months after primary infection, 20 persons were inoculated with the heterologous serotype. Only one person inoculated with a heterologous serotype at 8 weeks showed development of a clinical infection with a maximum temperature of 38 C, and 7 (88%) of 8 persons inoculated with a heterologous serotype at 4-9 months post-primary infection showed development of fever. On average, persons had a shorter incubation period in secondary infection compared with primary infection.

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“…Studies on children with ADEM show that two-thirds recover completely over the course of several weeks. 8,11 In 2007, the International Pediatric Multiple Sclerosis Study Group proposed the presence of encephalopathy, multifocal affectation, and the absence of previous demyelinating events as diagnostic criteria for ADEM, all of which are present in this patient. 3,10 The diagnosis of ADEM in this patient was supported by remission of signs following treatment with intravenous methylprednisolone.…”

Section: Discussionmentioning

confidence: 99%

“…1 This fact may support the hypothesis of genetic predisposition to develop ADEM; however, genome-wide association studies are required from a large populationbased research. 11 There is no standard treatment for ADEM. Steroids are used in high doses and diverse protocols use methylprednisolone or dexamethasone for 3-5 days, followed by oral steroids Figure 1.…”

Section: Discussionmentioning

confidence: 99%

Madariaga Virus Infection Associated with a Case of Acute Disseminated Encephalomyelitis

Luciani¹,

Abadía²,

Martínez-Torres³

et al. 2015

The American Society of Tropical Medicine and Hygiene

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Abstract. We present the first report of a pediatric case of acute disseminated encephalomyelitis (ADEM) associated with Madariaga virus infection (MADV, Alphavirus, Togaviridae; formerly known as South American variants of eastern equine encephalitis virus [EEEV]) in a patient of the 2010 alphaviral epidemic reported in Panama. The patient was admitted to the Hospital del Niñ o in Panama City with suspected meningitis, exhibited with decreased alertness and disorientation in space and time, hemiparesis, and left Babinski sign. The patient was transferred to the intensive care unit and treated with aciclovir and methylprednisolone. The magnetic resonance imaging (MRI) of the brain revealed multiple hyperintense lesions at T 2 -weighted images (T2) and fluid-attenuated inversion recovery (FLAIR) on the cortical-subcortical level. Sera samples obtained on days 6 and 12 were immunoglobulin M (IgM) positive for MADV. The findings on the clinical and cerebrospinal analyses, rapid symptom progression as well as neuroimaging, and serologic studies support our diagnosis. Our results suggest that MADV should be included in the etiologic differential diagnosis of ADEM in endemic countries.

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Genome-wide association study identifies susceptibility loci for dengue shock syndrome at MICB and PLCE1

Cited by 189 publications

References 32 publications

PLCε1 regulates SDF-1α–induced lymphocyte adhesion and migration to sites of inflammation

PLCε1 regulates SDF-1α–induced lymphocyte adhesion and migration to sites of inflammation

Research on Dengue During World War II Revisited

Madariaga Virus Infection Associated with a Case of Acute Disseminated Encephalomyelitis

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