免疫・アレルギーに興味のある学生・研究者・医師の皆様へ
京大小児科免疫・アレルギーグループの理念
免疫・アレルギー疾患は日進月歩の分野であり、この十年の間にも原因が不明とされていた多くの疾患でその原因・病態が明らかになり、新たな免疫抑制治療や生物学的製剤の導入により患者さんのＱＯＬも格段に向上してきました。一方でこのような疾患を正確に診断、適切な治療をする上では患者さんの病歴や症状・所見を詳細に把握し、考察する熟練した臨床能力が要求されます。また世界標準的な先進的医療をするためには一般的な臨床検査のみならず、病状に即した研究室レベルの分子生物学的解析を組み合わせることが重要と考えております。
もちろん、未だ十分な診断・治療が確立していない疾患、病態が明らかになっていない疾患も山積しております。一般的な疾患であるアトピー性皮膚炎や気管支喘息から難治性の慢性疾患である炎症性腸疾患、さらには希少疾患である自己炎症性疾患に至るまでその炎症がいかにおこるか？という病態はついては多くは不明のままです。このような疾患に関しても症例を集積し、最新技術を導入した研究を続けることで新たな展開を確立していけると信じております。
京大小児科免疫・アレルギーグループの活動
京大小児科免疫・グループではあらゆる小児免疫・アレルギー疾患を幅広く診療しており、小児リウマチ・アレルギー専門医、指導医取得までの様々なニーズに即した臨床研修を受けることのできる体制が整っています。また一般の分子生物学的解析をはじめ、次世代シーケンサーによる網羅的遺伝子解析、疾患特異的 iPS 細胞を用いた病態解析など、先端テクノロジーを応用した研究活動を行っています。具体的には不明熱・原発性免疫不全症の活動のリンクをご参照ください。
京大小児科免疫・アレルギーグループにご相談ください
京大小児科免疫・アレルギーグループでは上記の理念・体制のもと、ベッドサイド（臨床）からベンチ（研究室）を統合した診療を行っています。現在患者の診療に苦慮されている方、一般病院の臨床に限界を感じ、先端診療に興味をもたれた方は気軽にお問い合わせください。
問い合わせ先、八角高裕(yasumi*kuhp.kyoto-u.ac.jp.*を@に変更してください)。

京大小児科免疫・アレルギーグループの 2009 年～2013 年 9 月までの論文実績
1.

Yoshioka T, Nishikomori R, Hara J, Okada K, Hashii Y, Okafuji I, Nodomi S, Kawai T, Izawa K, Ohnishi H,Yasumi T, Nakahata T, Heike T. Autosomal Dominant Anhidrotic Ectodermal Dysplasia withImmunodeficiency Caused by a Novel NFKBIA Mutation, p.Ser36Tyr, Presents with Mild Ectodermal
Dysplasia and Non-Infectious Systemic Inflammation. J Clin Immunol. 2013 Oct;33(7):1165-74.

2.

Wada T, Sakakibara Y, Nishimura R, Toma T, Ueno Y, Horita S, Tanaka T, Nishi M, Kato K, Yasumi T, OharaO, Yachie A. Down-regulation of CD5 expression on activated CD8(+) T cells in familial hemophagocytic
lymphohistiocytosis with perforin gene mutations. Hum Immunol. 2013 Sep 16.

3.

Yokota S, Nishikomori R, Takada H, Kikuchi M, Nozawa T, Kanetaka T, Kizawa T, Miyamae T, Mori M,Heike T, Hara T, Imagawa T. Guidance on the use of canakinumab in patients with cryopyrin-associatedperiodic syndrome in Japan. Mod Rheumatol. 2013 May;23(3):425-9.

4.

Taniuchi S, Nishikomori R, Iharada A, Tuji S, Heike T, Kaneko K. MEFV Variantsin Patients with PFAPA
Syndrome in Japan. Open Rheumatol J. 2013 Apr 19;7:22-5.

5.

Imagawa T, Nishikomori R, Takada H, Takeshita S, Patel N, Kim D, Lheritier K, Heike T, Hara T, Yokota S.
Safety and efficacy of canakinumab in Japanese patients with phenotypes of cryopyrin-associated periodic
syndrome as established in the first open-label, phase-3 pivotal study (24-week results). Clin Exp Rheumatol.
2013 Mar-Apr;31(2):302-9. Epub 2013 Feb 1. PubMed PMID: 23380020.

6.

Kusunoki T, Morimoto T, Sakuma M, Mukaida K, Yasumi T, Nishikomori R, Heike T. Effect of eczema on theassociation between season of birth and food allergy in Japanese children. Pediatr Int. 2013 Feb;55(1):7-10.

7.

Abe J, Izawa K, Nishikomori R, Awaya T, Kawai T, Yasumi T, Hiragi N, Hiragi T, Ohshima Y, Heike T.
Heterozygous TREX1 p.Asp18Asn mutation can cause variable neurological symptoms in a family with
Aicardi-Goutieres syndrome/familial chilblain lupus. Rheumatology (Oxford). 2013 Feb;52(2):406-8.

8.

Kawai M, Yoshikawa T, Nishikomori R, Heike T, Takahashi K. Obvious optic disc swelling in a patient withcryopyrin-associated periodic syndrome. Clin Ophthalmol. 2013;7:1581-5.

9.

Yanagimachi MD, Niwa A, Tanaka T, Honda-Ozaki F, Nishimoto S, Murata Y, Yasumi T, Ito J, Tomida S,Oshima K, Asaka I, Goto H, Heike T, Nakahata T, Saito MK. Robust and highly-efficient differentiation offunctional monocytic cells from human pluripotent stem cells under serum- and feeder cell-free conditions.
PLoS One. 2013;8(4):e59243.

10. Mizuno T, Sakai H, Nishikomori R, Oshima K, Ohara O, Hata I, Shigematsu Y, Ishige T, Tamura K, Arakawa
H. Novel mutations of MVK gene in Japanese family members affected with hyperimmunoglobulinemia Dand periodic fever syndrome. Rheumatol Int. 2012 Dec;32(12):3761-4.
11. Hiejima E, Yasumi T, Kubota H, Ohmori K, Ohshima K, Nishikomori R, Nakase H, Chiba T, Heike T. Gastriculcer and gastroenteritis caused by Epstein-Barr virus during immunosuppressive therapy for a child withsystemic juvenile idiopathic arthritis. Rheumatology (Oxford). 2012 Nov;51(11):2107-9.
12. Tsumura M, Okada S, Sakai H, Yasunaga S, Ohtsubo M, Murata T, Obata H, Yasumi T, Kong XF, Abhyankar
A, Heike T, Nakahata T, Nishikomori R, Al-Muhsen S, Boisson-Dupuis S, Casanova JL, Alzahrani M, Shehri
MA, Elghazali G, Takihara Y, Kobayashi M. Dominant-negative STAT1 SH2 domain mutations in unrelated

patients with Mendelian susceptibility to mycobacterial disease. Hum Mutat. 2012 Sep;33(9):1377-87.
13. Tanaka T, Takahashi K, Yamane M, Tomida S, Nakamura S, Oshima K, Niwa A, Nishikomori R, Kambe N,Hara H, Mitsuyama M, Morone N, Heuser JE, Yamamoto T, Watanabe A, Sato-Otsubo A, Ogawa S, Asaka I,Heike T, Yamanaka S, Nakahata T, Saito MK. Induced pluripotent stem cells from CINCA syndrome patientsas a model for dissecting somatic mosaicism and drug discovery. Blood. 2012 Aug 9;120(6):1299-308.
14. Kawai T, Saito M, Nishikomori R, Yasumi T, Izawa K, Murakami T, Okamoto S, Mori Y, Nakagawa N, ImaiK, Nonoyama S, Wada T, Yachie A, Ohmori K, Nakahata T, Heike T. Multiple reversions of an IL2RG
mutation restore T cell function in an X-linked severe combined immunodeficiency patient. J Clin Immunol.
2012 Aug;32(4):690-7.
15. Aoyama K, Amano H, Takaoka Y, Nishikomori R, Ishikawa O. Cryopyrin-associated periodic syndrome: acase report and review of the Japanese literature. Acta Derm Venereol. 2012 Jul;92(4):395-8.
16. Horiuchi H, Shirakawa R, Yasumi T. [Molecular mechanism of granule secretion from platelet]. RinshoKetsueki. 2012 Jul;53(7):664-71. Review. Japanese.
17. Kawai T, Nishikomori R, Izawa K, Murata Y, Tanaka N, Sakai H, Saito M, Yasumi T, Takaoka Y, Nakahata T,Mizukami T, Nunoi H, Kiyohara Y, Yoden A, Murata T, Sasaki S, Ito E, Akutagawa H, Kawai T, Imai C,Okada S, Kobayashi M, Heike T. Frequent somatic mosaicism of NEMO in T cells of patients with X-linked
anhidrotic ectodermal dysplasia with immunodeficiency. Blood. 2012 Jun 7;119(23):5458-66.
18. Kawai T, Nishikomori R, Heike T. Diagnosis and treatment in anhidrotic ectodermal dysplasia withimmunodeficiency. Allergol Int. 2012 Jun;61(2):207-17.
19. Nishi M, Nishimura R, Suzuki N, Sawada A, Okamura T, Fujita N, Kanai R, Yano J, Adachi S, Yasumi T, Sato
E, Yasutomo K, Ishii E, Ohga S. Reduced-intensity conditioning in unrelated donor cord blood transplantation
for familial hemophagocytic lymphohistiocytosis. Am J Hematol. 2012 Jun;87(6):637-9.
20. Kusunoki T, Mukaida K, Morimoto T, Sakuma M, Yasumi T, Nishikomori R, Heike T. Birth order effect onchildhood food allergy. Pediatr Allergy Immunol. 2012 May;23(3):250-4.
21. Izawa K, Hijikata A, Tanaka N, Kawai T, Saito MK, Goldbach-Mansky R, Aksentijevich I, Yasumi T,Nakahata T, Heike T, Nishikomori R, Ohara O. Detection of base substitution-type somatic mosaicism of theNLRP3 gene with >99.9% statistical confidence by massively parallel sequencing. DNA Res. 2012
Apr;19(2):143-52.
22. Ohnishi H, Teramoto T, Iwata H, Kato Z, Kimura T, Kubota K, Nishikomori R, Kaneko H, Seishima M,Kondo N. Characterization of NLRP3 variants in Japanese cryopyrin-associated periodic syndrome patients. JClin Immunol. 2012 Apr;32(2):221-9.
23. Hiejima E, Komatsu H, Takeda Y, Sogo T, Inui A, Okafuji I, Nishikomori R,Nakahata T, Fujisawa T. Acuteliver failure in young children with systemic-onset juvenile idiopathic arthritis without macrophage activation
syndrome: report of two cases. J Paediatr Child Health. 2012 Mar;48(3):E122-5.
24. Mizukami T, Obara M, Nishikomori R, Kawai T, Tahara Y, Sameshima N, Marutsuka K, Nakase H, Kimura N,Heike T, Nunoi H. Successful treatment with infliximab for inflammatory colitis in a patient with X-linked
anhidrotic ectodermal dysplasia with immunodeficiency. J Clin Immunol. 2012 Feb;32(1):39-49.
25. Mukaida K, Kusunoki T, Morimoto T, Sakuma M, Yasumi T, Nishikomori R, Heike T. [Diagnosis andconsultation rates of allergic diseases in 11-year old schoolchildren, and usefulness of allergy screening test atschool]. Arerugi.2012 Jan;61(1):41-50. Japanese.
26. Sakai H, Okafuji I, Nishikomori R, Abe J, Izawa K, Kambe N, Yasumi T, Nakahata T, Heike T. The
CD40-CD40L axis and IFN-γ play critical roles in Langhans giant cell formation. Int Immunol. 2012
Jan;24(1):5-15.
27. Hiejima E, Nakase H, Uemoto S, Heike T. Esophageal foreign body causing sustained stridor in an infant.
Clin J Gastroenterol, 2012. 5(2):p.146-9.
28. Hiejima E, Komatsu H, Sogo T, Inui A, Fujisawa T. Utility of simplified criteria for the diagnosis ofautoimmune hepatitis in children. J Pediatr Gastroenterol Nutr, 2011.52(4):p470-3.
29. Ishimura M, Takada H, Doi T, Imai K, Sasahara Y, Kanegane H, Nishikomori R, Morio T, Heike T, Kobayashi
M, Ariga T, Tsuchiya S, Nonoyama S, Miyawaki T, Hara T. Nationwide survey of patients with primary
immunodeficiency diseases in Japan. J Clin Immunol. 2011 Dec;31(6):968-76.
30. Tahara M, Sakai H, Nishikomori R, Yasumi T, Heike T, Nagata I, Inui A, Fujisawa T, Shigematsu Y, NishijimaK, Kuwakado K, Watabe S, Kameyama J. Patient with neonatal-onset chronic hepatitis presenting withmevalonate kinase deficiency with a novel MVK gene mutation. Mod Rheumatol. 2011 Dec;21(6):641-5.
31. 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, Aróstegui JI, YagüeJ, Merino R, Ibañez M, Pontillo A, Takada H, Imagawa T, Kawai T, Yasumi T, Nakahata T, Heike T. Highincidence of NLRP3 somatic mosaicism in patients with chronic infantile neurologic, cutaneous, articularsyndrome: results of an International Multicenter Collaborative Study. Arthritis Rheum. 2011
Nov;63(11):3625-32.
32. Imamura M, Kawai T, Okada S, Izawa K, Takachi T, Iwabuchi H, Yoshida S, Hosokai R, Kanegane H,Yamamoto T, Umezu H, Nishikomori R, Heike T, Uchiyama M, Imai C. Disseminated BCG infection
mimicking metastatic nasopharyngeal carcinoma in an immunodeficient child with a novel hypomorphic
NEMO mutation. J Clin Immunol. 2011 Oct;31(5):802-10.
33. Karakawa S, Okada S, Tsumura M, Mizoguchi Y, Ohno N, Yasunaga S, Ohtsubo M, Kawai T, Nishikomori R,
Sakaguchi T, Takihara Y, Kobayashi M. Decreased expression in nuclear factor-κB essential modulator due toa novel splice-site mutation causes X-linked ectodermal dysplasia with immunodeficiency. J Clin Immunol.
2011 Oct;31(5):762-72.
34. Ohta H, Miyashita E, Hirata I, Matsumura R, Yoshida H, Hashii Y, Higashiura T, Yasumi T, Murata Y, Heike T,Yang X, Kanegane H, Ohara O, Ozono K. Hematopoietic stem cell transplantation with reduced intensity
conditioning from a family haploidentical donor in an infant with familial hemophagocytic lymphohistocytosis.
Int J Hematol. 2011 Sep;94(3):285-90.
35. Murata Y, Yasumi T, Shirakawa R, Izawa K, Sakai H, Abe J, Tanaka N, Kawai T, Oshima K, Saito M,
Nishikomori R, Ohara O, Ishii E, Nakahata T, Horiuchi H, Heike T. Rapid diagnosis of FHL3 by flow
cytometric detection of intraplatelet Munc13-4 protein. Blood. 2011 Aug 4;118(5):1225-30.
36. Watanabe T, Sato M, Gohda F, Takahashil Y, Uchiyama T, Maezawa A, Nishikomori R, Tamura J. [Casereport; a case of familial Mediterranean fever diagnosed in adult]. Nihon Naika Gakkai Zasshi. 2011 Apr

10;100(4):1041-3. Japanese.
37. Kusunoki T, Morimoto T, Sakuma M, Mukaida K, Yasumi T, Nishikomori R, Fujii T, Heike T. Total andlow-density lipoprotein cholesterol levels are associated with atopy in schoolchildren. J Pediatr. 2011Feb;158(2):334-6.
38. Adachi M, Watanabe A, Nishiyama A, Oyazato Y, Kamioka I, Murase M, Ishida A, Sakai H, Nishikomori R,Heike T. Familial cases of periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis syndrome.
J Pediatr. 2011 Jan;158(1):155-9.
39. Nishikomori R. [Recent new findings in autoinflammatory syndrome]. Nihon Rinsho Meneki Gakkai Kaishi.
2011;34(5):327-8. Japanese. PubMed PMID: 22348214.
40. Mukaida K, Kusunoki T, Morimoto T, Yasumi T, Nishikomori R, Heike T, Fujii T, Nakahata T. The effect ofpast food avoidance due to allergic symptoms on the growth of children at school age. Allergol Int. 2010
Dec;59(4):369-74.
41. Nagai K, Yamamoto K, Fujiwara H, An J, Ochi T, Suemori K, Yasumi T, Tauchi H, Koh K, Sato M, Morimoto
A, Heike T, Ishii E, Yasukawa M. Subtypes of familial hemophagocytic lymphohistiocytosis in Japan based ongenetic and functional analyses of cytotoxic T lymphocytes. PLoS One. 2010 Nov 30;5(11):e14173.
42. Kambe N, Nakamura Y, Saito M, Nishikomori R. The inflammasome, an innate immunity guardian,participates in skin urticarial reactions and contact hypersensitivity. Allergol Int. 2010 Jun;59(2):105-13.
43. Kusunoki T, Morimoto T, Nishikomori R, Yasumi T, Heike T, Mukaida K, Fujii T, Nakahata T. Breastfeeding
and the prevalence of allergic diseases in schoolchildren: Does reverse causation matter? Pediatr AllergyImmunol. 2010 Feb;21(1 Pt 1):60-6.
44. Sakai H, Ito S, Nishikomori R, Takaoka Y, Kawai T, Saito M, Okafuji I, Yasumi T, Heike T, Nakahata T. A
case of early-onset sarcoidosis with a six-base deletion in the NOD2 gene. Rheumatology (Oxford). 2010
Jan;49(1):194-6.
45. Kawabata H, Murakami M, Nishikomori R, Saito M, Takaoka Y, Nanao K, Maezawa M. A Japanese case offamilial Mediterranean fever with a MEFV gene mutation. Hokkaido Igaku Zasshi. 2009 Nov;84(6):419-22.
46. Kusunoki T, Morimoto T, Nishikomori R, Heike T, Fujii T, Nakahata T. Allergic status of schoolchildren withfood allergy to eggs, milk or wheat in infancy. Pediatr Allergy Immunol. 2009 Nov;20(7):642-7.
47. Kusunoki T, Morimoto T, Nishikomori R, Yasumi T, Heike T, Fujii T, Nakahata T. Changing prevalence andseverity of childhood allergic diseases in kyoto, Japan, from 1996 to 2006. Allergol Int. 2009 Dec;58(4):543-8.
48. Nakamura Y, Kambe N, Saito M, Nishikomori R, Kim YG, Murakami M, Núñez G, Matsue H. Mast cells
mediateneutrophil

recruitment

andvascularleakagethrough

theNLRP3

inflammasomeinhistamine-independent urticaria. J Exp Med. 2009 May 11;206(5):1037-46.
49. Okada S, Konishi N, Tsumura M, Shirao K, Yasunaga S, Sakai H, Nishikomori R, Takihara Y, Kobayashi M.
Cardiac infiltration in early-onset sarcoidosis associated with a novel heterozygous mutation, G481D, inCARD15. Rheumatology (Oxford). 2009 Jun;48(6):706-7.
50. 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. Role of the NOD2 genotype in the clinical phenotype ofBlau syndrome and early-onset sarcoidosis. Arthritis Rheum. 2009 Jan;60(1):242-50.