研究者業績
基本情報
- 所属
- 藤田医科大学 医学部 小児科 教授総合アレルギーセンター 副センター長
- 学位
- 博士(医学)(藤田保健衛生大学)
- J-GLOBAL ID
- 200901050027932873
- researchmap会員ID
- 1000360715
研究分野
1論文
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子どもの健康科学 25(1) 29-37 2024年1月【背景・目的】学校では教職員が複数児童の対応を同時に行うため、食物アレルギーに関するインシデントが起きやすい。2014年度に文部科学省から「学校給食における食物アレルギー対応指針」(以下、対応指針)が発表されたが、対応指針発表の前後におけるインシデント発生の背景因子を検証した報告はないため、今回我々は検討した。【方法】2015年度から2019年度に食物アレルギー講習会に参加した教員や保護者へ手渡し、あるいはアレルギー支援ネットワークのホームページのインシデント事例入力サイトや患者会への郵送などを通して、インシデント事例のアンケートを実施した。その中から教育施設に関する事例について対応指針発表前(15件)と発表後(28件)の2群に分けて、原因食品、誘発症状、発症状況、給食の対応レベル、生活管理指導表の提出状況、発症原因を調査した。【結果】インシデント事例の原因食品については鶏卵の割合が減り、発症状況については給食中が最多で変化はなかった。給食の対応レベルで「完全除去」よりも「一部弁当」や「普通食」の報告が増えていた。発症の原因として「完全除去」での「調理中のアレルゲン混入」の報告は減っていたが「配膳ミス」の報告は継続していた。運動誘発による事例が対応指針発表後、新たに報告され、昼食後の体育や遊び時間での発症が多く、重篤な症状も多く報告されていた。【結論】対応指針発表後もインシデントの背景因子として「配膳ミス」が報告されていることから、「配膳ミス」を防ぐ取り組みの推進と、新たな課題として食物依存性運動誘発アナフィラキシーの認知度を教育関係者に高める啓発活動が必要であると考えた。(著者抄録)
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International archives of allergy and immunology 1-6 2023年10月18日BACKGROUND: Allergen-specific immunotherapy (AIT), an established treatment for allergic diseases, prevents the development of other allergic manifestations. Although the mechanisms remain unclear, AIT has been shown to reduce basophil activation (BA) against nontarget allergens. OBJECTIVES: The aim of this study was to assess immunological changes in Dermatophagoides farinae (Der f) after Japanese cedar pollen (JCP)-based subcutaneous immunotherapy (SCIT) monotherapy. METHOD: The data of 16 patients (age: 6-37 years) with JCP-induced allergic rhinitis who were sensitive to Der f (serum Der f-specific immunoglobulin E [IgE] level >0.34 kUA/L) and received JCP-based SCIT for 5 years were reviewed retrospectively. BA by Der f and JCP extracts and serum-specific IgE and immunoglobulin G4 (IgG4) levels against these allergens were evaluated before and after completing 5 years of JCP-based SCIT monotherapy. RESULTS: The areas under the dose-response curves of BA by Der f and JCP extracts were significantly reduced (p = 0.02 and p = 0.002, respectively). JCP-specific IgE levels decreased and JCP-specific IgG4 levels increased significantly (p < 0.001 for both), whereas Der f-specific IgE and IgG4 levels did not change significantly. CONCLUSIONS: JCP-based SCIT monotherapy reduced Der f-specific BA. These findings suggest that JCP-based SCIT has the potential to modulate immune response toward nontarget allergens.
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Journal of Allergy and Clinical Immunology 152(1) 126-135 2023年7月 査読有り
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Clinical risk factors at 3 months of age for the development of bronchial asthma at 36 months of agePediatrics International 2023年3月17日
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アレルギー 72(2) 151-153 2023年3月即時型食物アレルギーの原因食物のうち、魚卵は5%で第6番目で、その95%はイクラである。アレルゲンとなる蛋白の種類そのものが異なる魚卵と鶏卵との間に交差抗原性はないが、魚卵間にはある。摂取状況を確認した検討では、イクラアレルギー患者においてタラコにも症状があるのは25%、子持ちシシャモに症状があるのは11%であった。イクラの主要アレルゲンはβ'-componentで、タラコとの交差抗原性に関与すると考えられた。
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Allergology international : official journal of the Japanese Society of Allergology 72(1) 182-184 2023年1月
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日本小児アレルギー学会誌 36(4) 412-412 2022年9月
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Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 33(9) e13850 2022年9月
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Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology 18(1) 49-49 2022年6月11日BACKGROUND: The Rosaceae family includes fruits, such as peach, apple, Japanese apricot, cherry (Prunoideae subfamily), and strawberry (Rosoideae subfamily). The allergens responsible for Rosaceae fruit allergies have been reported to include Bet v 1 and profilin, which mainly cause oral symptoms, and lipid transfer protein (LTP). Recently, gibberellin-regulated protein (GRP) has been identified as an allergen that induces generalized symptoms in peach-, orange-, and plum-related allergies. Most patients with food allergies induced by GRP show allergic symptoms accompanied by cofactors, such as exercise or drugs. To date, there are very few reports of generalized symptoms induced by strawberry. CASE PRESENTATION: We evaluated the reactivity of strawberry GRP in a 15-year-old boy who was confirmed to have generalized symptoms induced by strawberry with exercise using an oral food challenge test (OFCT). The patient's serum exhibited a strong positive reaction to strawberry GRP but not to peach GRP or peach LTP. The patient's basophils reacted to strawberry and peach GRP but not to peach LTP. CONCLUSIONS: Strawberry GRP may be a causative component for strawberry with exercise-induced generalized symptoms in this patient. This is the first study to investigate the role of GRP in strawberry with cofactor-induced allergic symptoms. Further epidemiological and clinical researches are necessary to improve diagnostic and therapeutic approaches for patients with strawberry allergy.
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日本小児体液研究会誌 14 17-23 2022年5月乳児のアトピー性皮膚炎(AD)では、重症例において電解質異常などの生命にかかわる合併症を呈することがある。症例は5ヵ月の男児。生後1ヵ月ごろから全身の湿疹が出現したが、家族のステロイド忌避により医療機関を受診せず、生後5ヵ月時の健診で重症湿疹と体重減少を指摘され当院に紹介入院した。身長58.7cm(-3.2SD)、体重4,140g(-4.4SD、1ヵ月前から-970g)、活気は乏しく、全身に浸出液を伴う湿疹がみられた。血液検査で著明な低Na血症(117mEq/L)・高K血症(8.3mEq/L)、低蛋白血症(Alb2.2g/dL)、腎機能障害(Cr 0.31mg/dL、eGFR 63.9ml/min/1.73m2)を認めた。また、FENa、FEKが低下していた一方で高レニン・高アルドステロン血症を認めた。輸液、フロセミド等の治療で電解質は正常化したが、体液貯留に伴う心不全がみられ、カテコラミン投与を要した。入院時の電解質異常の機序は、重症ADによる皮膚からのNa喪失により低Na血症が生じ、さらに遠位尿細管へのNa供給が低下することで、アルドステロン作用によるNa-Kの交換が不十分となり、高K血症が生じたと考えられた。初期治療後に心不全が生じたのはRefeeding syndromeによる体液貯留や、たこつぼ型心筋症、さらにアルブミン投与による循環血液量増加によるものと考えられた。(著者抄録)
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Fujita medical journal 8(2) 52-58 2022年5月Objectives: Fish roe is a common allergen in Japan. We have previously reported that although immunoglobulin (IgE) from patients with salmon roe (SR) or pollock roe (PR) allergies cross-react, 70% of patients with SR allergy can consume PR without developing any symptoms. However, a correlation between clinical cross-reactivity and serological cross-reactivity remains to be demonstrated. Methods: Serum samples were collected from 15 patients with SR allergy who had consumed cooked PR previously. Among these volunteers, four had experienced immediate symptoms after consuming cooked PR, while the others had exhibited no symptoms of PR allergy. A competitive enzyme-linked immunosorbent assay (ELISA) was performed to analyze the serological cross-reactivity with SR and PR. Immunoblotting inhibition assays were performed using serum samples that had been pre-incubated with SR or PR extracts. Results: In ELISAs, binding to SR was inhibited by >50% when the serum samples from patients with both SR and PR allergies were pre-incubated with PR extract (p=0.0256). In immunoblots, pre-incubation of serum samples with PR extract inhibited detection of the 16-kDa protein, which likely corresponds to the major SR allergen beta' component, significantly more for samples from patients with both SR and PR allergies (100%) than for samples from those with only an SR allergy (18.2%) (p=0.011). Conclusions: The superior competitive binding of the sera from patients with both SR and PR allergies to PR compared with that to SR may induce clinical cross-reactivity between SR and PR.
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別府大学大学院紀要 (24) 93-100 2022年3月2018年度に愛知県内病院を受診した魚アレルギー患者149名を対象に、魚種別摂取状況について質問紙調査を行った。さらに各魚の魚特異IgE抗体価の測定を行った。また、何らかの魚アレルギーの明らかなエピソードをもち、摂取可否の確認と摂取できる魚の検索を行うことに同意が得られた患者47例を対象に、食物経口負荷試験を実施した。質問紙調査は、明らかなエピソードが認められた105名を有効回答とした。「症状あり」と回答した魚種はサケ、タラ、タイが多く、「症状なし」の回答に、ツナ缶詰、カジキ、はんぺんなどの加工品が多くあげられた。魚の系統的分類は筋肉の色による原因魚の傾向はみられなかった。ツナ缶詰、カジキは食物経口負荷試験を安全に施行できる場合が多く、摂取可能な魚の探索に役立つものと考えられた。ツナ缶詰のZ scoreはマグロCAP-FEIA値と相関が見られた。
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Pediatrics international : official journal of the Japan Pediatric Society 64(1) e15163 2022年1月
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Journal of nutritional science and vitaminology 68(3) 221-227 2022年In this study, monoclonal antibodies against two major fruit allergens-gibberellin-regulated protein (GRP) and lipid transfer protein (LTP)-were established. Sandwich enzyme-linked immunosorbent assays (ELISAs) for the quantification of peach GRP and LTP were constructed using these antibodies. Both ELISAs reacted with the respective antigens when heated at 100ºC for 20 min, but not when reduced with sodium sulfite, indicating that GRP and LTP are heat-stable, while disulfide bonds play an important role in their native steric structures. GRP and LTP in peaches and peach-containing foods were quantified by these ELISAs. In both cases, there were few differences among peach cultivars normally available on the market; however, concentrations were higher when the peach was ripe. GRP was localized in the pulp of the peach, while LTP was present in the peel. They could be quantified in peach-containing beverages, as well as in dried and canned peaches. GRP in Japanese apricots could also be determined using this ELISA, as its amino acid sequence is the same as that of peach GRP. Then, high concentrations of GRP were detected in umeboshi, a traditional Japanese pickled apricot. Peach leaves were found to have a high LTP content, accordingly, LTP was also observed in lotions containing peach leaf extract. The ability to quantitatively detect GRP and LTP in this study will, therefore, contribute to the improvement of component-resolved diagnoses and quality of life in patients allergic to peaches.
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Allergologia et immunopathologia 50(2) 89-92 2022年BACKGROUND: Pollen-food allergy syndrome (PFAS) usually manifests as an itching sensation in the mouth and throat immediately after eating fresh fruits and vegetables. However, some patients with PFAS experience systemic symptoms including anaphylaxis. In Europe, cypress gibberellin-regulated protein (GRP) has been noted to cause allergenicity and exhibit cross-reactivity with peach GRP. Japanese cedar (Cryptomeria japonica), classified in the cypress family, is the primary causative substance among all environmental allergens in Japan. However, studies on the prevalence of GRP sensitization in patients with cedar pollinosis are lacking. OBJECTIVE: This study examined the prevalence of GRP sensitization in patients with Japanese cedar pollinosis. METHODS: We enrolled 52 patients who had requested sublingual immunotherapy treatment with mild-to-severe rhinitis during spring, and had a JCP-specific immunoglobulin E (IgE) levels of >0.7 UA/mL. Peach GRP was purified using affinity chromatography with a monoclonal antibody column. Specific IgE levels to peach GRP were measured using an enzyme-linked immunosorbent assay. Samples exhibiting absorbance at 450 nm of over mean plus three standard deviations of the negative control value were defined as positive. Sera from three patients with severe peach allergy were used as positive controls. RESULTS: Eleven sera from 52 patients with JCP-induced allergic rhinitis were positive for peach GRP. CONCLUSION: Twenty percent of patients with cedar pollinosis were sensitized to peach GRP. Well-powered studies are needed to clarify whether these patients are at an increased risk for systemic symptoms or whether they primarily demonstrate only localized symptoms.
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食物アレルギー研究会会誌 21(2) 56-59 2021年9月魚の主要アレルゲンであるパルブアルミンは魚種間で共通抗原性を有するため、魚アレルギー患者は複数の魚種に対して症状を示し、全ての魚の除去を指示されることもあることから、著者らは、魚アレルゲンを一般的に使用されている食品加工酵素で処理し、低アレルゲン化した魚肉エキスを作製し治療することを考えた。今回、開発した低アレルゲンサケエキスを用いた経口免疫療法を、サケを含む複数の魚種に対してアレルギーを有する5歳以上の魚アレルギー患者11名を対象に、プラセボを用いたランダム化比較試験として多施設共同で実施している。治療効果については、比較試験の途中であるためまだ公表できないが、治療を開始した11例のうち、治療食品の味の問題で治療を中止した1例を除き、10例で大きな副反応なく治療を継続できている。
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Asia Pacific allergy 11(2) e14 2021年4月An 8-year-old boy with poor control of atopic dermatitis could eat potato products such as French fries without restrictions until 21 months of age. However, he developed generalized urticaria after eating potato products at the same age. Therefore, potatoes were excluded from his diet; nevertheless, he continued to consume a very small amount of potato starch but was without symptoms until the age of 8 years. At this age, he developed anaphylaxis after consuming potato starch and required administration of intramuscular epinephrine. He tested positive for potato-specific immunoglobulin E, skin prick test, and basophil activation test. He developed severe eczema with dry skin and erosion. We later discovered that potato starch had been used for play clay at his nursery school. Although he discontinued using potato starch play clay, it remained present in his surroundings for 6 years. His potato allergy may have developed and continued to worsen as a result of making indirect contact with surfaces that had previously been exposed to the allergen. Two-dimensional Western blot analysis on potato starch revealed the presence of proteins binding to the immunoglobulin E of the patient. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis findings showed that 5 of the 6 protein bands had a similar molecular weight as that of potato proteins. Thus far, there are no reports of anaphylaxis due to potato starch. Children with atopic dermatitis or damaged skin may have sensitivity to potato starch and could develop anaphylaxis as noted in this case.
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別府大学大学院紀要 (23) 103-108 2021年3月柑橘類アレルギー患者を対象に、好塩基球活性化試験(BAT)の有用性について検討した。柑橘類に明らかなアレルギーの既往のある患者10名(男性1名、女性9名、年齢5〜32歳)および対照1名を対象とした。症状の誘発原因となった柑橘類はオレンジや温州ミカンが最も多く、グレープフルーツやレモンも原因となっていた。BATにて濃度依存的に抗原刺激したCD203cおよびCD63発現量の変化に関して、患者2名を除いた8名は重症度にかかわらずすべて20%を超える活性となった。多くは抗原濃度に従って上昇傾向を示し、一部は抗原濃度1mg/mLがピークであった。特に患者8はCD203cがほぼ陰性であったにもかかわらず、CD63で柑橘3種ともに最大活性が70%を超えていた。CD203cの発現が低い場合でもCD63で発現が認められたことで、CD63を加えたBATの有用性が明らかとなった。
MISC
606-
Allergology International 2020年© 2020 Japanese Society of Allergology Five years have passed since the Japanese Pediatric Guideline for Food Allergy (JPGFA) was first revised in 2011 from its original version. As many scientific papers related to food allergy have been published during the last 5 years, the second major revision of the JPGFA was carried out in 2016. In this guideline, food allergies are generally classified into four clinical types: (1) neonatal and infantile gastrointestinal allergy, (2) infantile atopic dermatitis associated with food allergy, (3) immediate-type of food allergy (urticaria, anaphylaxis, etc.), and (4) special forms of immediate-type of food allergy such as food-dependent exercise-induced anaphylaxis and oral allergy syndrome (OAS). Much of this guideline covers the immediate-type of food allergy that is seen during childhood to adolescence. Infantile atopic dermatitis associated with food allergy type is especially important as the onset of most food allergies occurs during infancy. We have discussed the neonatal and infantile gastrointestinal allergy and special forms of immediate type food allergy types separately. Diagnostic procedures are highlighted, such as probability curves and component-resolved diagnosis, including the recent advancement utilizing antigen-specific IgE. The oral food challenge using a stepwise approach is recommended to avoid complete elimination of causative foods. Although oral immunotherapy (OIT) has not been approved as a routine treatment by nationwide insurance, we included a chapter for OIT, focusing on efficacy and problems. Prevention of food allergy is currently the focus of interest, and many changes were made based on recent evidence. Finally, the contraindication between adrenaline and antipsychotic drugs in Japan was discussed among related medical societies, and we reached an agreement that the use of adrenaline can be allowed based on the physician's discretion. In conclusion, this guideline encourages physicians to follow the principle to let patients consume causative foods in any way and as early as possible.
講演・口頭発表等
84所属学協会
7共同研究・競争的資金等の研究課題
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