近藤 康人

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.

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。

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.

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.

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。

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.

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.

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。

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.

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。