Marhaeny Honey Dzikri, Rohmah Lutfiatur, Pratama Yusuf Alif, Kasatu Salsabilla Madudari, Miatmoko Andang, Addimaysqi Rafi, van den Bogaart Geert, Ho Franz Y, Taher Muhammad, Khotib Junaidi
Department of Pharmacy Practice, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia.
Department of Pharmaceutical Science, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia.
PLoS One. 2024 Dec 27;19(12):e0315312. doi: 10.1371/journal.pone.0315312. eCollection 2024.
Food allergies are a global health problem that continues to grow annually, with a prevalence of more than 10%. Shrimp allergy is the most common and life-threatening allergy. There is no cure for food allergies, but shrimp allergen extract (SAE) offers promise as a treatment through allergen-specific immunotherapy (AIT). However, whether SAE induces immunological tolerance in seafood allergies remains to be established. This study aimed to determine the effectiveness of SAE in inducing immunological tolerance in a gastro-food allergy mouse model. For the immunotherapy evaluation, mice (n = 24) were intraperitoneally (i.p.) sensitized with 1 mg alum and 100 μg SAE in PBS on days 0, 7, and 14 and randomly divided into four groups of six: a negative control (NC) and high- to low-dose immunotherapy (HI, MI, and LI). The untreated group (n = 6) only received 1 mg alum in PBS (i.p.). All groups were challenged with 400 μg SAE (i.g.) on days 21, 22, 23, 53, and 58. Following the challenge, SAE-sensitized mice from the immunotherapy group were treated (i.p.) with 10 μg SAE for LI, 50 μg SAE for MI, and 100 μg SAE for HI on days 32, 39, and 46. The untreated and NC groups only received PBS (i.p.). All mice were euthanized on day 59. As the results, we found that SAE immunotherapy reduced systemic allergy symptom scores, serum IL-4 levels, IL-4 and FcεR1α mRNA relative expression, and mast cell degranulation in ileum tissue in allergic mice while increasing Foxp3 and IL-10 mRNA relative expression. Notably, we observed an increased ratio of IL-10 to IL-4 mRNA expression, demonstrating the efficacy of SAE immunotherapy in promoting desensitization. Thus, SAE can be developed as an immunotherapeutic agent for food allergies by inducing prolonged allergy tolerance with a wide range of allergen targets.
食物过敏是一个全球性的健康问题,且其患病率每年都在持续上升,目前已超过10%。虾过敏是最常见且危及生命的过敏反应。食物过敏无法治愈,但虾过敏原提取物(SAE)有望通过过敏原特异性免疫疗法(AIT)成为一种治疗方法。然而,SAE是否能在海鲜过敏中诱导免疫耐受仍有待确定。本研究旨在确定SAE在胃食物过敏小鼠模型中诱导免疫耐受的有效性。为进行免疫疗法评估,在第0、7和14天,用1毫克明矾和100微克SAE于磷酸盐缓冲液(PBS)中对24只小鼠进行腹腔注射致敏,并随机分为四组,每组6只:阴性对照组(NC)以及高、中、低剂量免疫治疗组(HI、MI和LI)。未治疗组(6只)仅接受1毫克明矾于PBS中的腹腔注射。所有组在第21、22、23、53和58天接受400微克SAE的灌胃激发。激发后,免疫治疗组中经SAE致敏的小鼠在第32、39和46天分别接受10微克SAE(LI组)、50微克SAE(MI组)和100微克SAE(HI组)的腹腔注射治疗。未治疗组和NC组仅接受PBS腹腔注射。所有小鼠在第59天安乐死。结果发现,SAE免疫疗法降低了过敏小鼠的全身过敏症状评分、血清白细胞介素 - 4(IL - 4)水平、IL - 4和高亲和力IgE受体α链(FcεR1α)mRNA相对表达以及回肠组织中的肥大细胞脱颗粒,同时增加了叉头框蛋白3(Foxp3)和IL - 10 mRNA相对表达。值得注意的是,我们观察到IL - 10与IL - 4 mRNA表达的比例增加,证明了SAE免疫疗法在促进脱敏方面的功效。因此,SAE可通过诱导对多种过敏原靶点的长期过敏耐受而被开发为食物过敏的免疫治疗药物。