原標(biāo)題：絲聚蛋白功能缺失突變與雞蛋和牛奶過敏持續(xù)相關(guān)
背景：表皮屏障蛋白-絲聚蛋白（FLG）的遺傳缺陷在濕疹和相關(guān)過敏性氣道疾病的病因中起著重要作用。然而，F(xiàn)LG中的功能缺失（LOF）突變是否會導(dǎo)致食物過敏的發(fā)生和持續(xù)仍存在爭議。
目的：這項研究測試了FLG LOF突變與多種食物過敏反應(yīng)的相關(guān)性，并調(diào)查了它們對早期食物過敏持續(xù)性的潛在影響。
方法：這項研究招募了890名已經(jīng)食物激發(fā)驗證的食物過敏兒童參加德國食物過敏遺傳學(xué)研究（GOFA）。684名兒童的縱向數(shù)據(jù)可用。所有兒童都具有臨床特征，包括他們對特定食物的過敏反應(yīng)，并對FLG中4種最常見的LOF突變（R501X、2282del4、R2447X和S3247X）進(jìn)行基因分型。使用德國多中心過敏研究隊列作為對照人群，通過邏輯回歸分析FLG突變與食物過敏之間的關(guān)聯(lián)。
結(jié)果：FLG突變與多種食物過敏相關(guān)，包括雞蛋（HE）、牛奶（CM）、花生、榛子、魚、大豆、腰果、核桃和芝麻，風(fēng)險估計相似。調(diào)整濕疹狀態(tài)后，效果仍然顯著。有趣的是，F(xiàn)LG突變增加了HE和CM過敏持續(xù)病程的風(fēng)險。
結(jié)論：這項研究表明FLG LOF突變會帶來任何食物過敏的風(fēng)險，而與濕疹無關(guān)。這些突變傾向于雞蛋和牛奶過敏的持續(xù)性，應(yīng)在評估耐受性發(fā)展時予以考慮。


原始出處
JACI                                                  
Filaggrin loss-of-functionmutations are associated with persistence of egg andmilk allergy
DOI: org/10.1016/j.jaci.2022.05.018
Abstract:
Background: A genetic defect in the epidermal barrier protein filaggrin (FLG) plays a major role in the etiology of eczema and associatedallergic airways diseases.However, it is still controversial to what extend loss-of-function (LOF)mutations in FLG contribute to the development and persistence of food allergies.
Objectives: This study tested association of FLG LOF mutations with allergic reactions to diverse foods and investigated their potential effect on the persistence of early food allergies.
Methods: This study recruited 890 children with challengeproven food allergy for the German Genetics of Food Allergy Study (GOFA). Longitudinal data were available for 684 children. All children were clinically characterized, including their allergic responses to specific foods, and genotyped for the 4 most common LOF mutations in FLG; R501X,2282del4,R2447X, and S3247X. Associations between FLG mutations and food allergies were analyzed by logistic regression using the German Multicenter Allergy Study cohort as the control population.
Results: FLG mutations were associated with allergies to diverse foods including hen’s egg (HE), cow’s milk (CM), peanut,hazelnut, fish, soy, cashew, walnut, and sesame with similar risk estimates. Effects remained significant after adjusting for the eczema status. Interestingly, FLG mutations increased the risk of a persistent course of HE and CM allergy.
Conclusions: Using the gold standard for food allergy diagnosis,this study demonstrates that FLG LOF mutations confer a risk of any food allergy independent of eczema. These mutations predispose to the persistence of HE and CM allergy and should be considered in the assessment of tolerance development.
First Author:
Birgit Kalb
Correspondence:
Max-Delbruck-Center, Robert-Rossle-Strasse 10, 13092 Berlin, Germany
2023-01-04 Article