原標(biāo)題：植物源性食物的I型過敏反應(yīng): 對主要花粉過敏原敏感的結(jié)果
　　花粉過敏患者在食用植物性食物(水果、蔬菜和香料)時(shí)也經(jīng)常出現(xiàn)過敏癥狀，某些花粉過敏與食物不耐受的關(guān)系，導(dǎo)致了臨床綜合征出現(xiàn)，如芹菜-艾蒿-樺樹花粉綜合征，蘋果-樺樹花粉綜合征，以及類似的現(xiàn)象。早在10多年前就有研究表明，與花粉和食物蛋白發(fā)生交叉反應(yīng)的IgE抗體可能是引起上述臨床現(xiàn)象的原因。
　　花粉過敏患者在食用植物性食物(水果、蔬菜和香料)時(shí)也經(jīng)常出現(xiàn)過敏癥狀。新的信息使我們能夠?qū)⒒ǚ?食物過敏綜合征歸因于IgE抗體對保守的植物過敏原的交叉反應(yīng)，這些過敏原在相關(guān)和不相關(guān)的植物物種以及不同的植物組織中表達(dá)。保守蛋白是指具有重要生物學(xué)功能的蛋白質(zhì)，其序列和/或結(jié)構(gòu)是保守的。引起花粉-食物交叉反應(yīng)的重要保守過敏原是肌動(dòng)蛋白結(jié)合蛋白profilin，它首先在樺樹花粉(Bet v 2)中被描述，而主要的樺樹花粉過敏原Bet v 1,與致病相關(guān)的植物蛋白高度同源。我們提出的假設(shè)是，空氣中花粉變應(yīng)原致敏是導(dǎo)致IgE抗體產(chǎn)生的主要事件，然后IgE抗體能夠與同源食物變應(yīng)原發(fā)生交叉反應(yīng)。這項(xiàng)研究總結(jié)了這一假設(shè)的證據(jù)。對多種過敏原編碼的互補(bǔ)DNA進(jìn)行了表征，并在異種表達(dá)體系中以重組過敏原的形式表達(dá)。這些過敏原的序列比較顯示了與保守蛋白的顯著同源性。主要的樺樹花粉變應(yīng)原Bet v1與植物受微生物侵襲時(shí)表達(dá)的蛋白(病原相關(guān)蛋白)具有顯著的序列同源性，而另一種樺樹花粉變應(yīng)原Bet v2可被鑒定為profilin。profilin被稱為保守的肌動(dòng)蛋白結(jié)合蛋白，也參與了真核生物的磷酸肌醇途徑。編碼Bet v1和Bet v2的cDNAs以及重組過敏原的可用性使我們能夠證明，水果、蔬菜和香料中的樺樹花粉同源蛋白與IgE抗體發(fā)生交叉反應(yīng)，導(dǎo)致花粉-食物過敏綜合征。利用Bet v1特異性單克隆抗體和血清IgE，用Bet v1 cDNA進(jìn)行Northern印跡，證實(shí)了蘋果中存在Bet v1同源變應(yīng)原。利用重組Bet v1和Bet v2進(jìn)行IgE抑制實(shí)驗(yàn)，可以在許多水果、蔬菜和香料中發(fā)現(xiàn)Bet v1和Bet v2同源過敏原的存在。發(fā)現(xiàn)榛子過敏是由于與Bet v 1和Bet v 2有IgE抗體交叉反應(yīng)的原因。雖然重組Bet v 1可以用來阻止IgE結(jié)合到相應(yīng)的榛子過敏原,但食物過敏原無法完全阻止IgE結(jié)合到花粉過敏原上,表明可交叉反應(yīng)的IgE抗體產(chǎn)生主要是由致敏花粉蛋白質(zhì)引起的。艾草花粉中含有一種60 ~ 65KD的成分，可能與艾草的主要過敏原Art v 1相同，最近被報(bào)道與芹菜、蘋果、花生、獼猴桃以及單子葉植物和雙子葉植物花粉中的同源過敏原發(fā)生交叉反應(yīng)。為了驗(yàn)證植物源性食物過敏主要是由于IgE抗體與花粉中存在的同源過敏原發(fā)生交叉反應(yīng)的假設(shè)，我們在實(shí)驗(yàn)動(dòng)物模型中以重組花粉過敏原為免疫原誘導(dǎo)了交叉反應(yīng)的IgE抗體。在小鼠和恒河猴中，用重組花粉過敏原Bet v1和Bet v2免疫動(dòng)物，可誘導(dǎo)IgE抗體與存在于水果和蔬菜中的同源過敏原發(fā)生交叉反應(yīng)。
　　此外，免疫Bet v2的恒河猴對芹菜提取物表現(xiàn)出皮膚反應(yīng)活性，提示交叉反應(yīng)IgE抗體的臨床意義。植物源性食物過敏是由對同源蛋白-花粉過敏原的初步致敏引起的，這一證據(jù)來自以下觀察：只有在花粉和植物體細(xì)胞組織內(nèi)表達(dá)的過敏原,如Bet v 1和Bet v 2,可以確定為花粉和植物源性食物交叉反應(yīng)的過敏原。三種主要的草花粉變應(yīng)原(I、II和V組)在花粉中特異性表達(dá)，而不在植物其他組織中表達(dá)。雖然95%以上對草花粉過敏的患者對這些過敏原有反應(yīng)，但到目前為止，還沒有一種過敏原可以被確定為植物源性食物中的過敏原蛋白。同樣，一些其他過敏原，如Bet v3，一種鈣結(jié)合樺樹花粉過敏原，也只在花粉中表達(dá)，還沒有被認(rèn)為是食物過敏原。
　　相比之下，樺樹花粉變應(yīng)原Bet v1和Bet v2及其同源物可在植物組織細(xì)胞中檢測到，而Bet v1和Bet v2在花粉-食物交叉反應(yīng)中占很大比例。Bet v 1和Bet v 2在花粉中的表達(dá)是高度上調(diào)的,尤其是在花粉成熟期,雖然在植物組織體細(xì)胞中這類蛋白質(zhì)含量很少,但還是認(rèn)為花粉是花粉-食物過敏患者的主要致敏物。
　　了解花粉和植物源性食品中存在的類似的IgE表位是導(dǎo)致花粉-食品過敏綜合征患者IgE抗體交叉反應(yīng)的原因，這可能有助于診斷和治療。用于診斷和治療食物過敏的提取物制備非常難，因?yàn)樗褪卟说牡鞍踪|(zhì)和碳水化合物含量相對較低，而且這些提取物中致敏成分不穩(wěn)定。事實(shí)上，在大量對食物過敏患者身上進(jìn)行的實(shí)驗(yàn)證實(shí)，植物源性食物中針對蛋白質(zhì)的IgE的高比例可以被同源花粉蛋白吸收。因此，考慮用與同源食物過敏原發(fā)生交叉反應(yīng)的重組花粉過敏原用于診斷和治療似乎是合理的?；ǚ圻^敏的成功治療可能會顯著減少相關(guān)的食物過敏癥狀。Bet v 1、Bet v 2或其他同源過敏原存在于某些植物源性食物中，這一知識可能還有助于臨床醫(yī)生將某些花粉和食物過敏的關(guān)聯(lián)性解釋為這兩種來源中存在交叉反應(yīng)決定因素。
延伸閱讀
JACI                                                    
Type I allergic reactions to plant-derived  food: A consequence of primary sensitization  to pollen allergens  
https://doi.org/10.1016/S0091-6749(96)80062-5
Patients with pollen allergy also frequently experience allergic symptoms on ingestion of plantderived foods (fruits, vegetables, and spices). 1-3 The association of certain pollen allergies with food intolerance has led to the definition of clinical  syndromes such as the celery-mugwort-birch pollen syndrome, the apple-birch pollen syndrome,and similar phenomena. More than 10 years ago, it was suggested that IgE antibodies that cross-react with pollen and food proteins could be responsible for the observed clinical phenomena.
New information allows us to attribute pollen-food allergy syndromes to the cross-reactivity of IgE antibodies to conserved plant allergens that are expressed in related and unrelated plant species and different plant tissues. The term conserved protein refers to proteins that fulfill important biologic functions and therefore are conserved in their sequence and/or structure. Prominent conserved allergens responsible for pollen-food cross-reactivities are  the actin-binding protein profilin, first described in  birch pollen (Bet v 2), 9"1~ and the major birch  pollen allergen, Bet v 1,11 which is highly homologous  to pathogenesis-related plant proteins.  We have developed the hypothesis that sensitization  to airborne pollen allergens represents the  primary event leading to the induction of IgE  antibodies that are then capable of cross-reacting  with homologous food allergens. This study summarizes evidence for this hypothesis.
Complementary DNAs coding for a number of allergens were characterized and expressed as recombinant allergens in heterologous expression systems. Sequence comparison of several of these allergens has revealed significant homology with conserved proteins. The major birch pollen allergen Bet v 1 showed significant sequence homology with proteins (pathogenesis-related proteins) that are expressed in plants on microbial attack, ~1  whereas another birch pollen allergen, Bet v 2,  could be identified as profilin. 9 Profilins are known  as conserved actin-binding proteins, ~2 which also  participate in the phosphoinositide pathway in  eukaryotes. 13 The availability of the cDNAs coding  for Bet v 1 and Bet v 2 and the recombinant  allergens has allowed us to demonstrate that homologous  proteins in fruits, vegetables, and spices  cross-react with IgE antibodies to the birch proteins,  leading to pollen-food allergy syndromes.  
The presence of a Bet v 1 homologous allergen in apples was demonstrated by Northern blotting  with the Bet v 1 cDNA by using Bet v 1 specific  monoclonal antibodies and serum IgE. 14 By using recombinant Bet v 1 and Bet v 2 for IgE inhibition experiments, as well as specific antibodies, the presence of Bet v 1 and Bet v 2 homologous  allergens could be demonstrated in numerous fruits, vegetables, and spices. 15"17 Allergy to hazelnuts was found to be due to IgE  antibodies that cross-react with Bet v 1 and Bet v  2.18 Although recombinant Bet v 1 could be used to  absorb IgE binding to the homologous hazelnut  allergen, the food allergens were not able to completely  block IgE binding to the pollen allergens,  indicating that the cross-reactive IgE antibodies  originate primarily from a sensitization to pollen  proteins. A 60 to 65 kd component present in mugwort pollen, possibly identical to the major mugwort allergen Art v 1, was recently described to cross-react with homologous allergens present in celery, apple, peanut, kiwi, and pollens from  monocot and dicot plants. 19 To test the hypothesis that allergy to plant-derived food is primarily due to IgE antibodies that cross-react with homologous allergens present in pollen, we induced cross-reactive IgE antibodies in experimental animal models by using recombinant pollen allergens as immunogens. In mice, as well as in rhesus monkeys, immunization of animals with recombinant pollen allergens, Bet v 1 and Bet v 2,induced IgE antibodies that cross-reacted with  homologous allergens present in fruits and vegetables.  
2~ Moreover, Bet v 2-immunized rhesus monkeys displayed skin reactivity in response to celery extracts, indicating the clinical relevance of the cross-reactive IgE antibodies. 22 Further evidence that allergy to plant-derived  food originates from a primary sensitization to  homologous pollen allergens comes from the observation  that only allergens, such as Bet v 1 and  Bet v 2, which are expressed in pollen and in  somatic plant tissues, 23 could be identified as crossreactive allergens in pollen and plant-derived food.  The three major grass pollen allergens (groups I, II, and V) are specifically expressed in pollen and not in other plant tissues. 24, 25 Although more than 95% of patients allergic to grass pollen react to these allergens, so far none of the allergens could be identified as allergenic proteins in plant-derived food. 26 Likewise, several other allergens such as Bet v 3, a calcium-binding birch pollen allergen, z7 are expressed exclusively in pollen and are not yet described as food allergens.  
~ In contrast, the birch pollen allergens Bet v 1 and Bet v 2 and their homologues, which are responsible for a great proportion of pollen-food cross-reactivities, can be detected in somatic plant tissues. The fact that the expression of Bet v 1 and  Bet v 2 is highly upregulated in pollen, particularly  during pollen maturation, 28, 29 whereas only tiny amounts of the proteins could be detected in  somatic plant tissues, also argues in favor of the idea that pollen is the primary sensitizing agent in  patients with pollen-food allergy. The knowledge that similar IgE epitopes present in pollen and plant-derived foods are responsible for the cross-reactivity of IgE antibodies in patients  with pollen-food allergy syndromes might be useful  for diagnostic and therapeutic purposes. Extracts for use in the diagnosis and treatment of food allergies are extremely difficult to prepare because of the rather low protein versus carbohydrate content of fruits and vegetables and because of the  instability of allergenic components in such extracts.  In fact, experiments performed in a large number of patients allergic to food corroborate that a high proportion of IgE directed against proteins in plant-derived foods can be absorbed with homologous pollen proteins.
It therefore appears reasonable to consider recombinant pollen allergens that cross-react with homologous food allergens for use in diagnosis and perhaps in treatment. It might be that successful treatment of the pollen allergy would result in a significant reduction of the associated food allergy symptoms.  The knowledge that Bet v 1, Bet v 2, or other homologous allergens are present in certain plant derived foods may additionally help the clinician to interpret the association of certain pollen and food allergies as being due to the presence of crossreactive  determinants in both sources.
Authors:
Rudolf Valenta, MD, and Dietrich Kraft, MD Vienna, Austria
　　創(chuàng)建過敏性疾病的科研、科普知識交流平臺，為過敏患者提供專業(yè)診斷、治療、預(yù)防的共享平臺。