Summary

Ses i 1 is a storage protein of the 2S albumin family with a molecular weight of 9 kDa. It is one of the major allergens found in the sesame seeds (Sesamum indicum). Ses i 1 is reported to be the most clinically-relevant allergen of sesame, that is associated with severe allergic reactions, especially anaphylaxis. Studies have shown statistically significant association of Ses i 1 sensitization with the presence of allergic symptoms (skin, respiratory, gastrointestinal [GI] and cardiovascular symptoms) in sesame-sensitized symptomatic children. It is also found to be highly resistant to heat (100℃) and harsh conditions of GI tract. Ses i 1 is found to be a better candidate for diagnosing true clinical sesame allergy, along with exhibiting better specificity compared to whole sesame sIgE. Also, it is considered to be the best parameter for detecting the positive outcomes of oral food challenge as compared to whole sesame sIgE or even skin prick test. Further, highly variable immunological cross-reactivity has been reported between several 2S albumins, which include Ses i 1 (sesame), Cor a 14 (hazelnut), Ara h 2 (peanut), Jug r 1 (English walnut), Ber e 1 (Brazil nut), Ana o 3 (Cashew nut), Pis v 1 (pistachio), and Bra n 1 (rapeseed).

Epidemiology

Worldwide distribution

Sesame allergy is considered as the ninth most common childhood food allergy in the United States (US) (1), with a prevalence of 0.21% reported as convincing sesame allergy based on reported symptoms and IgE sensitization in a population-based survey. The prevalence of sesame allergy in adults in the US was found similar to that of children (0.24%) (2). In countries such as Canada and Mexico, the prevalence of self-reported sesame allergy has been estimated to be 0.1% (3, 4). In a high consumption country such as Australia, prevalence confirmed by oral food challenge (OFC) in infants has been found to be 0.8% (5). In the Middle east, where sesame also is widely consumed, sesame allergy is more common. In Israel for example, sesame allergy is the third most common food allergen and second most common food to cause anaphylaxis in children accounting for 43% of cases (6, 7), and with a prevalence of 0.93% confirmed sesame allergy (8). Furthermore, according to the Pronuts study on nut and sesame allergic children performed in the United Kingdom (UK) and Europe, 60% have more than one nut or seed allergy and sesame was responsible for allergy in 9.8% of nut-allergic children (9).

Ses i 1 is a storage protein of the 2S albumin family (10) and is one of the major allergens of sesame (Sesamum indicum) (11). In a study conducted in Italy among 10 patients with sesame allergy (severe generalized reactions), 100% of the patients showed positive immunoglobulin E (IgE) reactivity towards Ses i 1 (11). Further, a study conducted in Japan among 92 patients sensitized to sesame, presence of specific IgE (sIgE) to Ses i 1 was reported in 55.4% of the children (12).

Environmental Characteristics

Source and tissue

Ses i 1, a 2S albumin storage protein, is extracted from the seeds of Sesamum indicum (sesame) (11, 13).

Gel filtration was used for purification of natural Ses i 1 from defatted sesame seed extract (11, 12). It was further separated by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) and characterized by mass spectrometry, followed by circular dichroism or FT-IR (Fourier transform infrared) spectroscopy (11, 13). The molecule can also be generated by recombinant systems in Escherichia coli (12).

Clinical Relevance

Disease severity

Ses i 1 is reported to be the most clinically relevant allergen of sesame, that is associated with severe allergic reactions, especially anaphylaxis (11). In a study in Japan, 92 sesame-sensitized children were divided into symptomatic (positive oral sesame challenge or convincing history, n=36) and asymptomatic (negative oral sesame challenge or sesame tolerant, n=56) patients. The results demonstrated a statistically significant association (p<0.0001) of Ses i 1 sensitization with the presence of allergic symptoms (skin, respiratory, gastrointestinal [GI] and cardiovascular symptoms) in symptomatic children (33 out of 36) as compared to asymptomatic children (18 out of 56). Further, it was also reported that sIgE levels of 3.96 kU/L was considered as optimal cut-off with 86.1% sensitivity and 85.7% specificity. The study also reported Ses i 1 to be more allergenic than Ses i 2 (the other 2S albumin of sesame) based on the high levels of sIgE to Ses i 1 being observed in the symptomatic children as compared to Ses i 2 (12).

Similarly, another study conducted in Japan among 90 sesame-sensitized children evaluating the results of OFC found significantly (p<0.001) higher levels of sIgE to Ses i 1 in OFC-positive patients (n=18) as compared to OFC-negative patients (n=72) (14). Additionally, a study performed in the Netherlands found detectable sIgE to Ses i 1 in 10 sesame-allergic patients (n=35) as compared to 3 sesame-tolerant patients (n=13) confirmed by either an OFC or physician diagnosis (15).

Molecular Aspects

Biochemistry

Ses i 1 is a protein with a molecular weight of 9 kDa, that belongs to the 2S albumin family of storage proteins, a member of the prolamin superfamily. The 2S albumins are small, water-soluble globular heterodimers. Their two subunits (8-10 kDa and 3-4 kDa) are connected by four disulfide linkages. They are highly abundant in the seed cells and helpful during germination due to their ability to donate nitrogen and sulfur (11, 16, 17). (pg: 78)

The allergen has demonstrated resistance to high heat (100℃) as well as stability to severe conditions of GI tract. The conformation of the allergenic epitopes of Ses i 1 was found to be highly stable up to a temperature of 100℃ at both acidic and neutral pH. The large subunit of Ses i 1 was found to be completely intact after gastric as well as duodenal digestion and was proposed to be the key player in the allergenic reactions due to Ses i 1 (13).

Isoforms, epitopes, antibodies

As of 26th February 2021, only one isoallergen of Ses i 1 i.e. Ses i 1.0101 has been identified and officially published by the World Health Organization (WHO) and International Union of Immunological Societies (IUIS) Allergen Nomenclature (10).

Cross-reactivity due to structural similarity

Cross-reactivity between the 2S albumins have not been reported to be much, and this is due to the lack of extensive similarity found between their structures (11). However, limited but highly variable immunological cross-reactivity has been reported between several 2S albumins, which include Ses i 1 (sesame), Cor a 14 (hazelnut), Ara h 2 (peanut), Jug r 1 (English walnut), Ber e 1 (Brazil nut), Ana o 3 (Cashew nut), Pis v 1 (pistachio), and Bra n 1 (rapeseed) (18) (pg: 152).

The sequence homology among several 2S albumins, including those from sesame, peanut, castor seed, soybean, mustard, buckwheat and other tree nuts has reported to be between 14% and 40% (12). Also, in a study, 40% of sequence homology was found between Ses i 1 and 2S albumin of sunflower seeds, castor bean and Brazil nut. Further, the sequence identity, as well as similarity with Ses i 1, was reported to be 43% and 93% for sunflower seeds, 41% and 65% for castor beans and 47% and 87% for Brazil nut, respectively (11).       

The sequence identity and similarity between the two 2S albumins of sesame Ses i 1 and Ses i 2 was reported to be 35% and 50%, and between Ses i 1 and Ara h 2 in peanut it was reported to be 27% and 44%, respectively (12). In addition to this, a similarity of 51% was observed between Ses i 1 and Ana o 3 in cashew nut (19).

Diagnostic Relevance

Disease severity

Compared to whole sesame sIgE, Ses i 1 is found to be a better candidate for diagnosing true clinical sesame allergy, along with exhibiting better specificity (20-22). Utility of specific IgE testing with Ses i 1 as an alternative to the OFC was investigated in a study from Israel on 42 children with suspected sesame allergy (23) . Levels of specific IgE to Ses i 1 differed significantly between allergic (n=27) and tolerant (n=15) patients and correlated to results of the basophil activation test (BAT). Used together, specific IgE to Ses i 1 and BAT yielded correct positive classifications for 25 of 27 sesame allergic patients and could decrease the need for OFC in sesame allergic patients.

 In another study performed in Israel from the same research group, sesame oral immunotherapy (OIT) was evaluated in 75 children (24). Full desensitization was achieved in 88.4% of the patients. In a subset of these OIT patients (n=16) and controls (n=11), the levels of specific IgE to Ses i 1 was measured and was shown to decrease in the OIT-treated patients compared to controls.

Detection of Ses i 1-sIgE levels in suspected sesame-allergic patients can help in reducing the number of OFC needed to confirm a clinical sesame allergy (12). This was demonstrated in a retrospective study conducted in Japan among 90 children with sesame allergy (suspected or confirmed) depicting reduced requirement of OFCs in patients with high levels of sIgE to Ses i 1. The study found 5% and 50% probability of a positive OFC with Ses i 1-sIgE levels of 0.13 kU/L and 32.0 kU/l, respectively. Further, Ses i 1-sIgE was proposed to be the best parameter for predicting positive outcomes of OFC as compared to whole sesame sIgE or even SPT (14).

Similarly, a retrospective study conducted in US evaluated OFC results of 341 patients with a probable allergy to sesame. Of those, the levels of Ses i 1-sIgE was evaluated in 30 patients, of whom 40% (n=12) showed positive OFC outcomes. Ses i 1-sIgE was significantly associated with positive OFC outcome, unlike SPT or sIgE in this subset of patients. However, it was further observed that 30% of the patients with positive testing of sIgE to Ses i 1 had negative OFC results, which was still found to be better as compared to sesame-sIgE (69%) or SPT (61%) (25).

Exposure

Sensitization to 2S albumin, Ses i 1, is considered to occur through the GI tract. High stability, as well as structural resistance due to cysteine residues, make it sustainable in the GI tract's harsh acidic environment. Hence, they can cross the gut mucosal barrier, interact with the immune system, and trigger an allergic response (13).

Compiled By

Author: Turacoz Healthcare Solutions

Reviewer: Dr Eva Södergren

Last Reviewed: June 2021