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J Clin Immunol. 2019 Mar 29. doi: 10.1007/s10875-019-00602-x. [Epub ahead of print]

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

Author information

1
Department of Clinical Immunology and Allergy, Royal Melbourne Hospital, Parkville, VIC, 3052, Australia. slade.c@wehi.edu.au.
2
Immunology Division, Walter and Eliza Hall Institute for Medical Research, Parkville, VIC, 3052, Australia. slade.c@wehi.edu.au.
3
Department of Medical Biology, The University of Melbourne, Parkville, VIC, 3010, Australia. slade.c@wehi.edu.au.
4
Department of Anatomical Pathology, The Alfred Hospital, Prahran, VIC, 3181, Australia.
5
Department of Medical Biology, The University of Melbourne, Parkville, VIC, 3010, Australia.
6
Population Health and Immunity, Walter and Eliza Hall Institute for Medical Research, Parkville, VIC, 3052, Australia.
7
Department of Clinical Immunology and Allergy, Royal Melbourne Hospital, Parkville, VIC, 3052, Australia.
8
Immunology Division, Walter and Eliza Hall Institute for Medical Research, Parkville, VIC, 3052, Australia.
9
Department of Medicine, The University of Melbourne, Parkville, VIC, 3010, Australia.

Abstract

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-κB 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-κB2 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.

KEYWORDS:

CVID; Immunodeficiency; NF-kappaB2 deficiency; NFKB2; encephalitis; enterovirus

PMID:
30927119
DOI:
10.1007/s10875-019-00602-x

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