Analysis of plant food allergen sequences showed that allergenic components belonged to only 27 of the identified food-derived more than 8,000 protein families, and these are as follows; 1) Prolamin superfamily, including prolamins, which have been identified in cereals; 2S albumins in peanut, tree nuts and mustard; non-specific lipid transfer proteins in all types of plant food and latex; and bifunctional-amylase/protease inhibitors in cereals. 2) Cupin family includes 7/8S globulins, which have been identified in legumes, nuts, seeds; and 11S globulins in peanut, tree nuts. 3) Profilin is the actin binding regular protein which has been identified in all types of plant food. 4) Bet v 1 related proteins (pathogenesis related proteins family 10, PR-10), which have also been identified in all types of plant food [33]. As mentioned above, peanut contains all of the major plant derived allergenic components, as well as sharing most of the sequences with allergenic legumes, nuts and other seeds. Since the 1990's, the use of lupine seeds has been increased, and lupine seed protein allergies have been reported and increased during 15 years. The more complex thing is that legumes (peanut, soybean, lentils, beans, chickpeas and peas) may cross-react with lupines in around 15-87% in cases, with or without clinical relevancies, so the evaluation of cross reactions, interferences or ostentations among these plant-derived foods components, is an interesting issue for future plant FA research [33]. Almost all cases of peanut allergy (PNA) is IgE-mediated disease, occurs in over 1% of children, and it has been tripled during last decade in the western countries [30, 34]. Considering the increasing incidences of severe forms of PNA, there are studies on allergen-specific immunotherapy, clinical and epidemiologic pattern of PNA, and diagnostic approaches for PNA in children without previous exposure are a rising research area, among others [29, 34-36]. In addition, fruits, grains and other plant derived food allergens are more important in some regions than in others. For example, sesame has been highlighted as a potent plant food allergen, and buckwheat flour is well known as a potent food allergen in Japan, Korea and several European countries, and the kiwi fruits are the important allergenic foods in some countries [14, 15, 17, 37, 38].

Although PNA is not prevalent in Asia as it is in the western countries, during recent 15 years, the incidences of PNA has been increased in Korea, especially in children. We evaluated the clinical symptoms and history of PNA and serum specific IgE to peanut and other major food allergens (ImmunoCAP; Phadia, Sweden) in 804 patients under the age of three [39]. The patients had moderate-to-severe atopic dermatitis, and were enrolled from January 2000 to December 2006 at Ajou University Hospital. Among them, 148 showed sensitization to peanut (>0.35 kU/L), and were then analyzed in detail based on information recorded on their patient logs, as well as additional information gathered through telephone surveys. For the clinical estimation of PNA, we used the cut-off values of peanut specific IgEs ≥ 15 kU/L. Our study reveals that the peanut sensitization rate in Korea reaches 18%, and that patients showed significant tendency to have co-sensitization with house dust mites, egg white, wheat, and soybean, when sensitized to peanut. The higher specific IgE to peanut was related to the likelihood of the patient to develop severe systemic reactions.

Walnut allergy (WNA) is also an important plant FA and is reported mainly in the western countries, while it is rarely reported in Asia. However, recently we reported a relatively large clinical study on WNA in Korean Children [40]. In the study, we focused on the clinical characteristics of WNA and co-senstization/cross-reactivity between walnut, peanut and pine nut in young Korean children (Table 1). This study is based on the analysis of data from 69 patients under 4 years of age, who have been suspected of having WNA and diagnosed with allergic disease at Ajou University Hospital, Suwon, from January 2009 to December 2010. Sera of all patients were analyzed for serum peanut-specific IgE, walnut-specific IgE, and pine nut-specific IgE (ImmunoCAP; Phadia, Sweden). Clinical details of patients were collected by medical history. In addition, we had produced walnut, peanut, and pine nut extracts, and ELISA inhibition tests were applied to the sera of patients. Twenty-nine (42%) were accompanied with atopic dermatitis, 15 (21.7%) with urticaria, 10 (14.5%) with anaphylaxis, 6 (8.7%) with angioedema, and 1 (1.5%) with asthma. Twenty-two (31.9%) were sensitized to WN (>0.35 kU/L, 0.45-27.4 kU/L), and among them, 10 (45.5%) were sensitized only to WN, 6 (27.3%) were co-sensitized with PN, 6 (27.3%) were co-sensitized with PN and pine nut. Using the IgE ELISA inhibition test, we confirmed that PN and WN has partial cross-reactivity with IgE binding capacity. Further investigation has been carried out for 31 selected clinical WNA cases aged 8~108 months, and sera from 26 patients were used for component-resolved diagnosis (CRD) by protein microarrays (ImmunoCAP ISAC-CRD 103; Phadia, Sweden). Jug r 1 is the only major allergenic component in Korean children with clinical WNA, and 40% of patients were co-sensitized to various nuts, without typical clinical manifestations [41].

There have been several studies on allergies to grains, such as buckwheat, rice and barley, in Korean children [42-46]. Buckwheat (BW) is considered to be one of the most important food allergens, and positive skin tests are found in about 5% of Korean children [17]. We investigated the positive and negative predictive values of BW-specific IgE in 28 children with challenge proven BW allergy and 16 asymptomatic control subjects, with positive skin test to BW [42]. According to the receiver operator characteristic analysis, the optimal cut-off level of BW-specific IgE, as the definitions of serum BW-specific IgE positive, was 1.26 kUA/L. With this selected cut off level, the sensitivity, specificity, positive and negative predictive values were 93.10, 93.33, 79.75 and 97.96%, respectively. Furthermore, we reported that 3 cases of nocturnal asthma in Korean children who used BW chaff-stuffed pillow for 3-7 years [43]. In all patients, BW sensitization was initiated by the BW chaff-stuffed pillow, and all three children showed positive skin reactions to BW, but none of them had positive reactions to house-dust mites. Nocturnal asthmatic symptoms were completely recovered during 7 days of pillow elimination, and asthmatic responses were provoked by bronchial challenge with BW extract. Thus in this study, we confirmed that a small amount of BW attached to chaff-stuffed pillow can induced BW sensitization, provoke asthma symptoms in children. And there was an immunological study on the identification and characterization of major allergenic components in Korean children and adults with BW allergy [44]. In this study, 19 BW allergic subjects with symptoms after BW ingestion and 15 asymptomatic control subjects with positive skin prick test to BW were recruited. BW-specific IgE was measured with the Pharmacia CAP system and allergenic components of BW were analyzed using two-dimensional PAGE, and sequencing of N-terminal amino acids. From the BW-allergic patients, the sensitivity (100%), specificity (53%), and negative (100%) and positive predictive values (73%) of Pharmacia CAP specific IgE for diagnosis were estimated. And the major allergenic components which bind to more than 50% of patients' sera were 24-kDa (pI 8.3), 16-kDa (pI 5.6), and 9-kDa (pI 5.0/6.0). However, the specific IgE to split 19-kDa (pI 6.5/7.0) allergens were more specifically found in BW-allergic patients than in the asymptomatic subjects. N-terminal amino-acid sequences of 19-kDa and 16-kDa allergens showed moderate and weak homology to the 19-kDa globulin protein of rice and amylase/trypsin inhibitor of millet, respectively. The N-terminus of the 9-kDa isoallergens were not different from each other and were identified as the reported trypsin inhibitors of BW. Attenuation of the IgE binding to the 9-kDa allergen was found with periodate oxidation.

Rice is a basic food which rarely causes FA in Korea. However there has been an increase of non-specific sensitization in Korean children, without clinical symptoms. So, we tried to determine the major IgE binding components in rice extract and their clinical significance [45]. Twenty-four children (15 boys and 9 girls; mean age, 16.3 months) with allergic disease, who were sensitized to rice antigen confirmed by ImmunoCAP in the Pediatric Allergy Respiratory Center at Soonchunhyang University Hospital, were enrolled. In this study, the IgE binding capacities of various types of rice (raw, cooked, and heat-treated, simulated gastric fluid, and simulated intestinal fluid) were investigated using SDS-PAGE and IgE immunoblot analysis. In SDS-PAGE, more than 16 protein bands were observed in the raw rice, whereas only 14-16 kDa and 31-35 kDa protein bands were observed in cooked rice. The common SDS-PAGE protein bands observed in SGF-, SIF-, and heat treated rice were 9, 14, and 31 kDa. In a heated-rice IgE immunoblot, protein bands of 9, 14, and 31-33 kDa were found in 27.8%, 38.9%, and 38.9% of all sera, respectively. Furthermore, the 9 kDa, 14 kDa and 31-kDa bands were IgE binding components in 50%-75% of sera from symptomatic rice allergic children, and hence, appeared to be the clinically relevant rice allergens in Korean children.

Recently we experienced 3 cases of barley allergic infants who became sensitized due to their infant diet containing barley flour. Among them, we reported the case of an 11-month old boy who experienced an episode of anaphylaxis due to ingestion of barley flour. [46]. The infant experienced generalized urticaria, periorbital swelling, wheezing and dyspnea 30 min after eating baby food powder, containing barley, chestnut, and rice. Laboratory tests demonstrated high total serum IgE (531 kU/L) and revealed high levels of IgE sensitizations to wheat (64.3 kU/L), barley (35.2 kU/L), and rice (1.39 kU/L), but the patient only had a clinical reaction to barley. Using the IgE-immunoblot assay, 7, 14, 25, and 26 kDa of IgE binding bands were identified, and a high degree of IgE crossreactivity between barley and wheat extracts were revealed using IgE-immunoblot inhibition and ELISA-inhibition tests. We recently evaluated the clinical characteristics of kiwi fruit allergy as well as kiwi specific IgE in Korean young children [47]. The study was based on data analysis of 18 patients, aged 11-108 months (median age 25 months), who were diagnosed with clinical kiwi fruit allergy at Ajou University Hospital from June 2005 to June 2012. Clinical details were collected by medical history and telephone survey. Twelve out of 18 (66.7%) were diagnosed with angioedema or urticaria, 4 (22.2%) were diagnosed with oral allergy syndrome, 1 was presented with dyspnea, and 1 was diagnosed with anaphylaxis by kiwi fruit. Oral route of exposure (88.9%) was most common and 89% of subjects experienced systemic reactions at the time of first exposure. Hence, from this study, we have established that kiwi fruit allergy is not rare in Korean children, and that systemic reactions are more common in younger patients. The kiwi fruit allergy in older children who are allergic to pollens and kiwi together should be evaluated.

In summary, although the systematic studies have not been performed as of yet, plant-derived food allergies are not rare in Korean children and clinical symptoms are comparably severe. Even in infants and young children, the allergies due to plant foods (such as soy, peanut, walnut and other tree nuts, wheat flour, buckwheat flour and other cereals, kiwi fruit and other fruits) are not rare, and the face that their prevalence seems to be increasing demands further consideration.