2011 Fiscal Year Final Research Report
Development of CINCA syndrome therapy based upon the pathophysiology of CINCA syndrome elucidated by cytoengineering.
Project/Area Number |
21390310
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pediatrics
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Research Institution | Kyoto University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
HEIKE Toshio 京都大学, 医学研究科, 教授 (90190173)
|
Co-Investigator(Renkei-kenkyūsha) |
OHARA Osamu かずさDNA研究所, ヒトゲノム究部 (20370926)
KAMBE Naotomo 千葉大学, 医学研究院, 准教授 (50335254)
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Project Period (FY) |
2009 – 2011
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Keywords | 小児免疫 / アレルギー / 膠原病 |
Research Abstract |
CINCA syndrome is an autoinflammatory disease with fever, urticarial rash, aseptic meningitis, and arthritis caused by NLRP3 gene mutations. It has been known that 40% of the CINCA syndrome patients lack NLRP3 mutations by Sanger sequencing. Recently we have reported"mutation-negative"CINCA syndrome can be caused by NLRP3 somatic mosaicism. In this study, we have collected"mutation-negative"CINCA patients worldwide and demonstrated that 69% of the"mutation-negative"CINCA patients are caused by NLRP3 mosaicism. We also developed an easier and less labor-intensive method to identify NLRP3 mosaicism by next-generation sequencing. Furthermore, we created induced pluripotent stem cells(iPSC) derived from CINCA syndrome and developed methods to differentiate the iPSC to macrophages and chondrocytes, which can be utilized for research on the elucidation of the pathophysiology of the CINCA syndrome.
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[Journal Article] Detection of Base Substitution-Type Somatic Mosaicism of the NLRP3 Gene with> 99. 9% Statistical Confidence by Massively Parallel Sequencing2012
Author(s)
Izawa, K., A. Hijikata, N. Tanaka, T. Kawai, M. K. Saito, R. Goldbach-Mansky, I. Aksentijevich, T. Yasumi, T. Nakahata, T. Heike, R. Nishikomori, and O. Ohara
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Journal Title
DNA Res
Volume: 19
Pages: 143-52
DOI
Peer Reviewed
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[Journal Article] Characterization of NLRP3 variants in Japanese cryopyrin-associated periodic syndrome patients2012
Author(s)
Ohnishi, H., T. Teramoto, H. Iwata, Z. Kato, T. Kimura, K. Kubota, R. Nishikomori, H. Kaneko, M. Seishima, and N. Kondo
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Journal Title
J Clin Immunol
Volume: 32
Pages: 221-9
DOI
Peer Reviewed
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[Journal Article] High incidence of NLRP3 somatic mosaicism in patients with chronic infantile neurologic, cutaneous, articular syndrome2011
Author(s)
Tanaka N, Izawa K, Saito MK, Sakuma M, Oshima K, Ohara O, Nishikomori R, Morimoto T, Kambe N, Goldbach-Mansky R, Aksentijevich I, de Saint Basile G, Neven B, van Gijn M, Frenkel J, Arostegui JI, Yague J, Merino R, Ibanez M, Pontillo A, Takada H, Imagawa T
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Journal Title
Arthritis Rheum
Volume: 63
Pages: 3625-32
DOI
Peer Reviewed
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[Journal Article] Familial cases of periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis syndrome2011
Author(s)
Adachi, M., A. Watanabe, A. Nishiyama, Y. Oyazato, I. Kamioka, M. Murase, A. Ishida, H. Sakai, R. Nishikomori, and T. Heike
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Journal Title
The Journal of pediatrics
Volume: 158
Pages: 155-9
DOI
Peer Reviewed
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[Journal Article] Patient with neonatal-onset chronic hepatitis presenting with mevalonate kinase deficiency with a novel MVK gene mutation2011
Author(s)
Tahara, M., H. Sakai, R. Nishikomori, T. Yasumi, T. Heike, I. Nagata, A. Inui, T. Fujisawa, Y. Shigematsu, K. Nishijima, K. Kuwakado, S. Watabe, and J. Kameyama
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Journal Title
Modern rheumatology the Japan Rheumatism Association
DOI
Peer Reviewed
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[Journal Article] Novel mutations of MVK gene in Japanese family members affected with hyperimmunog lobulinemia D and periodic fever syndrome2011
Author(s)
Mizuno, T., H. Sakai, R. Nishikomori, K. Oshima, O. Ohara, I. Hata, Y. Shigematsu, T. Ishige, K. Tamura, and H. Arakawa
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Journal Title
DOI
Peer Reviewed
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[Journal Article] Enhanced NF-kappa activation with aninflammasome activator correlates with activity of auto inflammatory disease associated with NLRP3 mutations outside of exon 32010
Author(s)
Kambe, N., Satoh, T., Tanizaki, H., Fujisawa, A., Saito, M. K. & Nishikomori, R
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Journal Title
Arthritis Rheum
Pages: 3124-3125
DOI
Peer Reviewed
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[Journal Article] Role of the NOD2 genotype in the clinical phenotype of Blau syndrome and early-onset sarcoidosis2009
Author(s)
Okafuji, I., Nishikomori, R., Kanazawa, N., Kambe, N., Fujisawa, A., Yamazaki, S., Saito, M., Yoshioka, T., Kawai, T., Sakai, H., Tanizaki, H., Heike, T., Miyachi, Y. & Nakahata, T.
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Journal Title
Arthritis Rheum
Volume: 60
Pages: 242-250
DOI
Peer Reviewed
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[Journal Article] Cardiac infiltration in early-on setsarcoi dosis associated with a novel heterozygous mutation2009
Author(s)
Okada, S., Konishi, N., Tsumura, M., Shirao, K., Yasunaga, S., Sakai, H., Nishikomori, R., Takihara, Y. & Kobayashi M
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Journal Title
CARD15 Rheumatology(Oxford)
Volume: 48
Pages: 706-707
DOI
Peer Reviewed
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[Journal Article] Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria2009
Author(s)
Nakamura, Y., Kambe, N., Saito, M., Nishikomori, R., Kim, Y. G., Murakami, M., Nunez, G. & Matsue, H.
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Journal Title
J Exp Med
Volume: 206
Pages: 1037-1046
DOI
Peer Reviewed
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[Presentation] High incidence of nlrp3 somatic mosaicism in chronic infantile neurological cutaneous andarticular syndrome patients : a report from an international multicenter collaborative study2011
Author(s)
R. Nishikomori, N. Tanikaze, K. Izawa, M. K. Saito, R. Goldbach-ManskyI. Aksentijevich, G. de Saint Basile, B. Neven, J. Frenkel, M. Van Gijn, J. I. Arostegui, J. Yague, T. Morimoto, M. Sakuma, N. Kambe, T. Yasumi, T. Kawai, A. Pontillo, K. Oshima, H. Tak
Organizer
OP0142 : Annual European Congress of Rheumatology EULAR
Place of Presentation
London, United Kingdom
Year and Date
20112528
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[Presentation] Diagnosis of nlrp3 somatic mosaicism incinca/nomid patients using next-generation sequencing : Poster Session, Board P292 : 18thEuropean Pediatric Rheumatology Congress2011
Author(s)
K. Izawa, A. Hijikata, R. Nishikomori, O. Ohara, J. Abe, N. Tanaka, M. K. Saito, R. Goldbach-Mansky, I. Aksentijevich, T. Kawai, T. Yasumi, T. Nakahata, T. Heike
Organizer
September
Place of Presentation
Bruges, Belgium
Year and Date
20111418
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