Fatal Enteroviral Encephalitis in a Patient with Common Variable Immunodeficiency Harbouring a Novel Mutation in NFKB2

被引:15
|
作者
Slade, Charlotte A. [1 ,2 ,3 ]
McLean, Catriona [4 ]
Scerri, Thomas [3 ,5 ]
Tran Binh Giang [1 ,2 ,3 ]
Megaloudis, Steven [1 ,2 ,3 ]
Strathmore, Alexander [1 ,2 ,3 ]
Tempany, Jessica C. [2 ,3 ]
Nicholls, Katherine [1 ]
D'Arcy, Colleen [4 ]
Bahlo, Melanie [3 ,5 ]
Hodgkin, Philip D. [2 ,3 ]
Douglass, Jo A. [1 ,6 ]
Bryant, Vanessa L. [1 ,2 ,3 ]
机构
[1] Royal Melbourne Hosp, Dept Clin Immunol & Allergy, Parkville, Vic 3052, Australia
[2] Walter & Eliza Hall Inst Med Res, Immunol Div, Parkville, Vic 3052, Australia
[3] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia
[4] Alfred Hosp, Dept Anat Pathol, Prahran, Vic 3181, Australia
[5] Walter & Eliza Hall Inst Med Res, Populat Hlth & Immun, Parkville, Vic 3052, Australia
[6] Univ Melbourne, Dept Med, Parkville, Vic 3010, Australia
关键词
Immunodeficiency; CVID; NFKB2; enterovirus; encephalitis; NF-kappaB2; deficiency; MENINGOENCEPHALITIS; AGAMMAGLOBULINEMIA; EPIDEMIOLOGY; NF-KAPPA-B2; DEFICIENCY; INFECTION; DIAGNOSIS; IMMUNITY;
D O I
10.1007/s10875-019-00602-x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Common variable immunodeficiency is the most prevalent of the primary immunodeficiency diseases, yet its pathogenesis is largely poorly understood. Of the cases that are monogenic, many arise due to pathogenic variants in NFKB1 and NFKB2. Here, we report enteroviral encephalomyelitis as the cause of a fatal neurodegenerative condition in a patient with a novel heterozygous mutation in NFKB2 (c.2543insG, p.P850Sfs36*) that disrupts non-canonical NF-kappa B signaling. Investigations of primary and secondary lymphoid tissue demonstrated a complete absence of B cells and germinal centers. Despite multiple negative viral PCR testing of cerebrospinal fluid during her disease progression, post-mortem analysis of cerebral tissue revealed a chronic lymphocytic meningoencephalitis, in the presence of Cocksackie A16 virus, as the cause of death. The clinical features, and progression of disease reported here, demonstrate divergent clinical and immunological phenotypes of individuals within a single family. This is the first reported case of fatal enteroviral encephalomyelitis in a patient with NF-kappa B2 deficiency and mandates a low threshold for early brain biopsy and the administration of increased immunoglobulin replacement in any patient with a defect in this pathway and deterioration of neurological status.
引用
收藏
页码:324 / 335
页数:12
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