原標(biāo)題：絲聚蛋白功能缺失突變與雞蛋和牛奶過(guò)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(guò)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(huì)導(dǎo)致食物過(guò)敏的發(fā)生和持續(xù)仍存在爭(zhēng)議。
目的：這項(xiàng)研究測(cè)試了FLG LOF突變與多種食物過(guò)敏反應(yīng)的相關(guān)性，并調(diào)查了它們對(duì)早期食物過(guò)敏持續(xù)性的潛在影響。
方法：這項(xiàng)研究招募了890名已經(jīng)食物激發(fā)驗(yàn)證的食物過(guò)敏兒童參加德國(guó)食物過(guò)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(duì)特定食物的過(guò)敏反應(yīng)，并對(duì)FLG中4種最常見(jiàn)的LOF突變（R501X、2282del4、R2447X和S3247X）進(jìn)行基因分型。使用德國(guó)多中心過(guò)敏研究隊(duì)列作為對(duì)照人群，通過(guò)邏輯回歸分析FLG突變與食物過(guò)敏之間的關(guān)聯(lián)。
結(jié)果：FLG突變與多種食物過(guò)敏相關(guān)，包括雞蛋（HE）、牛奶（CM）、花生、榛子、魚(yú)、大豆、腰果、核桃和芝麻，風(fēng)險(xiǎn)估計(jì)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?cè)黾恿薍E和CM過(guò)敏持續(xù)病程的風(fēng)險(xiǎn)。
結(jié)論：這項(xiàng)研究表明FLG LOF突變會(huì)帶來(lái)任何食物過(guò)敏的風(fēng)險(xiǎn)，而與濕疹無(wú)關(guān)。這些突變傾向于雞蛋和牛奶過(guò)敏的持續(xù)性，應(yīng)在評(píng)估耐受性發(fā)展時(shí)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