近藤 康人

Patients with peach allergy who experience severe symptoms, including anaphylaxis, reportedly have a higher positivity for peach gibberellin-regulated protein (GRP)-specific immunoglobulin (Ig) E than those with only oral symptoms. However, a study in Italy investigating apple allergy (another Rosaceae fruit) found no clear association between apple GRP-specific IgE levels and clinical disease types. This study aimed to evaluate the clinical utility of GRP-specific IgE measurement in Japanese patients with apple allergy. We collected sera from apple-allergic patients in Japan and measured their IgE levels specific to apple GRP. Apple-allergic patients (14 with oral reactions and 14 with systemic reactions) and seven non-allergic controls were examined. The specific IgE levels against apple, Mal d 1, Mal d 4, Japanese cedar, Japanese alder, Japanese white birch, Bet v 1, and Bet v 2 were also determined using 3gAllergy™. Positive results for apple-GRP-specific IgE by enzyme-linked immunosorbent assay were obtained in one patient with oral reactions and in seven cases of systemic reactions. Exercise as a cofactor was involved in cases with high apple GRP-specific IgE. GRP expression was considerably lower in apples than in peaches, as detected by reverse transcription-quantitative polymerase chain reaction testing. Thus, GRP-specific IgE may be an important marker for diagnosing systemic reactions triggered by exercise in fruits with low GRP expression, such as apples.

BACKGROUND: Walnut (Juglans regia) frequently triggers nut allergies in the United Kingdom and in the United States, with increasing cases in Japan. While oral food challenges (OFCs) are the definitive method for diagnosing these allergies, they pose the risk of symptom provocation, necessitating safer alternative tests. Our aim here was to evaluate the diagnostic utility of IgE (immunoglobulin E) crosslinking-induced luciferase expression (EXiLE) for walnut allergy compared with the walnut-specific IgE (sIgE) test, Jug r 1-sIgE test, and skin prick test (SPT). METHODS: This retrospective study analyzed 55 patients tested for walnut allergy (WA) at Fujita Health University Bantane Hospital from January 2021 to December 2023. Among them, 38 had allergic reactions to walnuts based on history or OFCs and 17 did not. We evaluated the sensitivity, specificity, positive predictive value, negative predictive value, and the area under the curve (AUC) of the receiver operating characteristic curve. RESULTS: The EXiLE method (AUC = 0.938) exhibited superior diagnostic accuracy compared to the walnut-sIgE and comparable performance to Jug r 1-sIgE and SPT. The optimal cutoff value of 1.26-fold change demonstrated high sensitivity (0.92), specificity (0.88), positive predictive value (0.92), and negative predictive value (0.82). The EXiLE method yielded positive results in all three cases with negative Jug r 1-sIgE (< 0.35 UA/mL). CONCLUSION: The EXiLE method showed high sensitivity and specificity for diagnosing WA, indicating its potential clinical utility. Furthermore, the combination of Jug r 1-sIgE and EXiLE may enhance diagnostic accuracy. Future large-scale studies are warranted to confirm these findings and establish comprehensive diagnostic protocols.

type:text 乳幼児健診を受診した１．６歳児１６０名（回答率９４．７％）、３歳児１６８名（回答率９７．１％）を対象とした。アレルギー検査を受けた経験は、１．６歳児で１７．５％（２８名）、３歳児で２２．６％（３８名）であった。アレルギー原因物質は、１．６歳児では９割が食物であるのに対して３歳児では花粉や動物の割合が高くなっていた。また、食物アレルギー児をもつ母親は授乳中（母乳栄養）に小麦製品の摂取頻度が少なく、乳製品を控える傾向にあった。

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 &gt;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 &lt; 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。