2020年10月20日
IRAK4 Deficiency Presenting with Anti-NMDAR Encephalitis and HHV6 Reactivation
Journal of Clinical Immunology
- 巻
- 41
- 号
- 1
- 開始ページ
- 125
- 終了ページ
- 135
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1007/s10875-020-00885-5
- 出版者・発行元
- Springer Science and Business Media {LLC}
<jats:title>Abstract</jats:title>
<jats:p>IRAK4 deficiency is an inborn error of immunity predisposing patients to invasive pyogenic infections. Currently, there is no established simple assay that enables precise characterization of <jats:italic>IRAK4</jats:italic> mutant alleles in isolation. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune condition that is characterized by psychiatric symptoms, involuntary movement, seizures, autonomic dysfunction, and central hypoventilation. It typically occurs in adult females associated with tumors. Only a few infantile cases with anti-NMDAR encephalitis have been so far reported. We identified a 10-month-old boy with IRAK4 deficiency presenting with anti-NMDAR encephalitis and human herpes virus 6 (HHV6) reactivation. The diagnosis of IRAK4 deficiency was confirmed by the identification of compound heterozygous mutations c.29_30delAT (p.Y10Cfs*9) and c.35G>C (p.R12P) in the <jats:italic>IRAK4</jats:italic> gene, low levels of IRAK4 protein expression in peripheral blood, and defective fibroblastic cell responses to TLR and IL-1 (TIR) agonist. We established a novel NF-κB reporter assay using IRAK4-null HEK293T, which enabled the precise evaluation of <jats:italic>IRAK4</jats:italic> mutations. Using this system, we confirmed that both novel mutations identified in the patient are deleterious. Our study provides a new simple and reliable method to analyze <jats:italic>IRAK4</jats:italic> mutant alleles. It also suggests the possible link between inborn errors of immunity and early onset anti-NMDAR encephalitis.</jats:p>
<jats:p>IRAK4 deficiency is an inborn error of immunity predisposing patients to invasive pyogenic infections. Currently, there is no established simple assay that enables precise characterization of <jats:italic>IRAK4</jats:italic> mutant alleles in isolation. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune condition that is characterized by psychiatric symptoms, involuntary movement, seizures, autonomic dysfunction, and central hypoventilation. It typically occurs in adult females associated with tumors. Only a few infantile cases with anti-NMDAR encephalitis have been so far reported. We identified a 10-month-old boy with IRAK4 deficiency presenting with anti-NMDAR encephalitis and human herpes virus 6 (HHV6) reactivation. The diagnosis of IRAK4 deficiency was confirmed by the identification of compound heterozygous mutations c.29_30delAT (p.Y10Cfs*9) and c.35G>C (p.R12P) in the <jats:italic>IRAK4</jats:italic> gene, low levels of IRAK4 protein expression in peripheral blood, and defective fibroblastic cell responses to TLR and IL-1 (TIR) agonist. We established a novel NF-κB reporter assay using IRAK4-null HEK293T, which enabled the precise evaluation of <jats:italic>IRAK4</jats:italic> mutations. Using this system, we confirmed that both novel mutations identified in the patient are deleterious. Our study provides a new simple and reliable method to analyze <jats:italic>IRAK4</jats:italic> mutant alleles. It also suggests the possible link between inborn errors of immunity and early onset anti-NMDAR encephalitis.</jats:p>
- リンク情報
-
- DOI
- https://doi.org/10.1007/s10875-020-00885-5
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/33083971
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846526
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85092899058&origin=inward 本文へのリンクあり
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85092899058&origin=inward
- ID情報
-
- DOI : 10.1007/s10875-020-00885-5
- ISSN : 1573-2592
- eISSN : 1573-2592
- ORCIDのPut Code : 82513934
- PubMed ID : 33083971
- PubMed Central 記事ID : PMC7846526
- SCOPUS ID : 85092899058