IRAK4 deficiency presenting with anti-NMDAR encephalitis and HHV6 reactivation
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 IRAK4 mutant alleles in isolation. Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an autoimmune...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Springer
2020
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| _version_ | 1797110195609927680 |
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| author | Nishimura, S Kobayashi, Y Ohnishi, H Moriya, K Tsumura, M Sakata, S Mizoguchi, Y Takada, H Kato, Z Sancho-Shimizu, V Picard, C Irani, S Ohara, O Casanova, J-L Puel, A Ishikawa, N Okada, S Kobayashi, M |
| author_facet | Nishimura, S Kobayashi, Y Ohnishi, H Moriya, K Tsumura, M Sakata, S Mizoguchi, Y Takada, H Kato, Z Sancho-Shimizu, V Picard, C Irani, S Ohara, O Casanova, J-L Puel, A Ishikawa, N Okada, S Kobayashi, M |
| author_sort | Nishimura, S |
| collection | OXFORD |
| description | 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 IRAK4 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 IRAK4 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 IRAK4 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 IRAK4 mutant alleles. It also suggests the possible link between inborn errors of immunity and early onset anti-NMDAR encephalitis. |
| first_indexed | 2024-03-07T07:51:55Z |
| format | Journal article |
| id | oxford-uuid:9595bcac-0ed8-4e91-9b21-4b6dac08ec79 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:51:55Z |
| publishDate | 2020 |
| publisher | Springer |
| record_format | dspace |
| spelling | oxford-uuid:9595bcac-0ed8-4e91-9b21-4b6dac08ec792023-07-21T09:10:47ZIRAK4 deficiency presenting with anti-NMDAR encephalitis and HHV6 reactivationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9595bcac-0ed8-4e91-9b21-4b6dac08ec79EnglishSymplectic ElementsSpringer2020Nishimura, SKobayashi, YOhnishi, HMoriya, KTsumura, MSakata, SMizoguchi, YTakada, HKato, ZSancho-Shimizu, VPicard, CIrani, SOhara, OCasanova, J-LPuel, AIshikawa, NOkada, SKobayashi, MIRAK4 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 IRAK4 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 IRAK4 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 IRAK4 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 IRAK4 mutant alleles. It also suggests the possible link between inborn errors of immunity and early onset anti-NMDAR encephalitis. |
| spellingShingle | Nishimura, S Kobayashi, Y Ohnishi, H Moriya, K Tsumura, M Sakata, S Mizoguchi, Y Takada, H Kato, Z Sancho-Shimizu, V Picard, C Irani, S Ohara, O Casanova, J-L Puel, A Ishikawa, N Okada, S Kobayashi, M IRAK4 deficiency presenting with anti-NMDAR encephalitis and HHV6 reactivation |
| title | IRAK4 deficiency presenting with anti-NMDAR encephalitis and HHV6 reactivation |
| title_full | IRAK4 deficiency presenting with anti-NMDAR encephalitis and HHV6 reactivation |
| title_fullStr | IRAK4 deficiency presenting with anti-NMDAR encephalitis and HHV6 reactivation |
| title_full_unstemmed | IRAK4 deficiency presenting with anti-NMDAR encephalitis and HHV6 reactivation |
| title_short | IRAK4 deficiency presenting with anti-NMDAR encephalitis and HHV6 reactivation |
| title_sort | irak4 deficiency presenting with anti nmdar encephalitis and hhv6 reactivation |
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