MengHeng Oum

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Maud Seguy

Catherine Ferrant

Ommar Swe Tin

National Management Degree College

Véronique Chevalier

Animal, Santé, Territoires, Risques et Ecosystèmes

Nguyễn Trần Hiển

National Institute Of Hygiene And Epidemiology

Kevin Bleakley

Laboratoire de Mathématiques d'Orsay

Marc Lecuit

Institut Pasteur

Khansoudaphone Phakhounthong

Mahosot Hospital

Sayaphet Rattanavong

Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit

Veasna Duong

Institut Pasteur du Cambodge

Cooperative Institutions

Inserm

Université Paris Cité

Rockefeller University

Institut des Maladies Génétiques Imagine

Centre National de la Recherche Scientifique

Assistance Publique – Hôpitaux de Paris

Institut Pasteur

Institut Pasteur du Cambodge

Mahosot Hospital

Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit

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A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity

The Journal of Experimental Medicine (2024)

Fahd Al Qureshah Jérémie Le Pen Nicole A. de Weerd Marcela Moncada‐Vélez Marie Materna

Autosomal recessive deficiency of the IFNAR1 or IFNAR2 chain of the human type I IFN receptor abolishes cellular responses to IFN-α, -β, and -ω, underlies severe viral diseases, and is globally very rare, except for IFNAR1 and IFNAR2 deficiency in Western Polynesia and the Arctic, respectively. We report 11 human IFNAR1 alleles, the products of which impair but do not abolish responses to IFN-α and -ω without affecting responses to IFN-β. Ten of these alleles are rare in all populations studied, but the remaining allele (P335del) is common in Southern China (minor allele frequency ≈2%). Cells heterozygous for these variants display a dominant phenotype in vitro with impaired responses to IFN-α and -ω, but not -β, and viral susceptibility. Negative dominance, rather than haploinsufficiency, accounts for this dominance. Patients heterozygous for these variants are prone to viral diseases, attesting to both the dominance of these variants clinically and the importance of IFN-α and -ω for protective immunity against some viruses.

Dominance (genetics)

Haploinsufficiency

Heterozygote advantage

10.1084/jem.20241413

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Childhood encephalitis in the Greater Mekong region (the SouthEast Asia Encephalitis Project): a multicentre prospective study

The Lancet Global Health (2022)

Jean‐David Pommier Chris Gorman Yoann Crabol Kevin Bleakley Heng Sothy

Encephalitis is a worldwide public health issue, with a substantially high burden among children in southeast Asia. We aimed to determine the causes of encephalitis in children admitted to hospitals across the Greater Mekong region by implementing a comprehensive state-of-the-art diagnostic procedure harmonised across all centres, and identifying clinical characteristics related to patients' conditions.

Acute disseminated encephalomyelitis

Viral encephalitis

10.1016/s2214-109x(22)00174-7

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