Typ:
Component
Komponente
Component
Tri a 14, nsLTP, Triticum aestivum
nonspecific lipid transfer protein type 1
f433
recombinant, CCD-free protein
Triticum aestivum (wheat) non-specific lipid transfer protein
Tri a 14 is a 9-kDa non-specific lipid transfer protein (nsLTP) present in the grains of Triticum aestivum (wheat). Tri a 14 sensitization has been associated with multiple clinical presentations, including food allergy to wheat with or without cofactor involvement, wheat-dependent exercise induced anaphylaxis, occupational baker’s asthma, and nsLTP syndrome. Clinically silent Tri a 14 sensitization is frequent.
T. aestivum grain, a cosmopolitan staple food, is associated with various adverse allergic and non-allergic reactions such as food allergy, baker’s asthma, contact urticaria, food protein-induced enterocolitis, eosinophilic esophagitis, and celiac disease [1]. T. aestivum flour contains a rich array of proteins. As of April 26, 2022, the IUIS/WHO Nomenclature comprises 28 allergens [2], out of a reported 70 IgE-binding wheat flour proteins [3].
Sensitization to wheat nsLTP Tri a 14 has been reported in patients from virtually all geographical areas, meaning that it is not limited to Mediterranean climate [4]. However, Tri a 14 sensitization is typically found in Mediterranean areas [4, 5]. Tri a 14 sensitization mainly affects adolescents and adults [6].
Tri a 14 is found in the whole grain, bran and flour of T. aestivum [7]. Wheat bran contains 4.5-fold higher amounts of Tri a 14 compared with flour [7]. Following protein extraction procedures from raw and cooked wheat, Tri a 14 is demonstrated in the water-soluble albumin/globulin fraction [8].
Sensitization to Tri a 14 occurs through wheat ingestion [6] but inhalation of Tri a 14 can result in occupational baker’s asthma [4].
Assessment of Tri a 14 specific IgE, in conjunction with ω-5 gliadin Tri a 19 and wheat extract is recommended in both food and inhalation-induced wheat allergy [3, 9]. Insufficient detection sensitivity of Tri a 14 IgE using multiplex methods has been reported [9].
Inhalation challenge tests have demonstrated that Tri a 14 sensitization is a cause of occupational asthma developing in up to 10% of people exposed to inhalation of wheat flour, also known as baker’s asthma [3, 10]. The reported prevalence of Tri a 14 sensitization in bakers with wheat-induced occupational asthma varied from 2.5% in German patients (continental temperate area) [11] to 25% in Korean patients [12], to 45% - 60% in Spanish patients (Mediterranean area) [13]. Specificity was also variable, with Tri a 14 sensitization lacking in Spanish controls (allergic rhinitis or wheat-induced food allergy) [14] but demonstrated in 10% of German controls [11]. Of note, small patient and control samples as well as different Tri a 14 isoallergens were used for these studies: Tri a 14.0101 in Spain, and Tri a 14.0201 in Germany [11]. A later study was performed with sera from both climate areas and with both Tri a 14 isoallergens, confirming a 3-21% prevalence of Tri a 14 sensitization baker’s asthma irrespective of the climate area [15]. Thus, the current view of Tri a 14 is that of a clinically important, but immunologically minor allergen in baker’s asthma.
Wheat-induced food allergy refers to reactions induced by wheat ingestion, with or without the contribution of a cofactor [16]. Severe allergic reactions upon wheat ingestion occurring only in association with exercise or physical exertion are identified as wheat-dependent exercise-induced anaphylaxis (WDEIA) [16]. Tri a 14 sensitization may be found in any type of wheat-induced food allergy: WDEIA or classical food allergy with urticaria, angioedema and potentially anaphylaxis, often in association with a nsLTP syndrome. However, Tri a 14 is not the predominant allergen in any of the wheat-induced food allergy presentations, nor in any geographical area [6, 8, 12, 16].
Further data on Tri a 14 associated with nsLTP syndrome and WDEIA are provided below.
The nsLTP syndrome refers to complex sensitization profiles comprising more than one nsLTP often associated with the immunodominant nsLTP Pru p 3 or Art v 3, which can translate into clinical reactivity to multiple pollen and plant foods [4, 6].
Tri a 14 sensitization may be associated to nsLTP syndrome [4, 17]. Cannabis use has also been associated with an apparently Can s 3-driven nsLTP syndrome comprising Tri a 14 sensitization [5]. In Mediterranean as well as non-Mediterranean patients, Tri a 14 sensitization did not exceed a prevalence of 30% and, as opposed to other nsLTPs, inconsistently correlated with sensitization to other members of the nsLTP family as reflected by conflicting study reports [4, 17, 18]. Allergic reactions to cereals such as wheat as part of a nsLTP syndrome are rare [19], with 68% of Tri a 14-sensitized patients with a nsLTP syndrome tolerant to wheat consumption [9].
WDEIA patients are more often sensitized to Tri a 19, the ω-5 gliadin, than to Tri a 14 [6, 12, 16]. Tri a 14 sensitization associated to WDEIA has been mainly reported in Mediterranean patients, adult as well as pediatric, and an associated history of Pru p 3-related peach allergy was reported [20, 21].
Tri a 14 sensitization was not associated with oral allergy syndrome in Mediterranean or non-Mediterranean areas [17, 18]. In a study conducted in Italian patients, Tri a 14 sensitization was correlated with a history of food-induced systemic reactions, with an odds ratio of 2.32 [18]. Taking a different approach based on sensitization to Tri a 14 or Tri a 19 as a classification criterion, followed by clinical history and evaluation of wheat-induced food allergy, the clinical relevance of Tri a 14 sensitization was better delineated [16]. This study showed that, in wheat-sensitized patients, Tri a 14 sensitization was most often a clinically silent finding (72% of 79 patients). Severe reactions to wheat ingestion were recorded in 19% of patients with Tri a 14 sensitization, as compared with 55% of those with Tri a 19 sensitization. Cofactor involvement was present in 16% of Tri 14 sensitized patients, while atopy was present in 67%. IgE levels to Tri a 14 were directly correlated to those measured to Pru p 3 and to whole allergen extracts of LTP-containing cereals (wheat, barley, oats, rye, maize, and rice) and nuts (peanut, hazelnut, walnut, and almond) [16].
Tri a 14, a member of the nsLTP family, exhibits moderate cross-reactivity with other nsLTPs, and is capable of inducing sensitization in the absence of Pru p 3 [6]. Importantly, Tri a 14 does not cross-react with grass pollen, and thus may help distinguish cross-reactivity between wheat and grass pollen from genuine wheat sensitization [6, 8]. Studies addressing Tri a 14 sensitization in the context of other allergenic nsLTPs showed that Tri a 14 is one of the most infrequent nsLTP sensitizations, both in Mediterranean and non-Mediterranean areas [4, 17, 18]. Tri a 14 sensitization shares with Ole e 7 and Par j 2 this relative independence from other nsLTPs [18].
Tri tu 14, a 9-kDa nsLTP from T. turgidum (durum wheat), exhibited significant cross-reactivity with Tri a 14 despite interindividual variability and a relatively low sequence identity of 49% [22]. Conversely, maize LTP displayed cross-reactivity with Tri a 14 in only 1/22 wheat-allergic patients, despite relatively high sequence identity at 59% [8].
Not relevant.
Tri a 14 is one of T. aestivum nsLTPs [1, 2], with a molecular weight of 9.1 kDa (isoallergen Tri a 14.0101) or 9.7 kDa (isoallergen Tri a 14.0201), and therefore recognized as a type 1 nsLTP. It displays a typical nsLTP secondary structure, made up of a majority of α helices which fold into a globular protein stabilized by four disulfide bonds and featuring an internal, hydrophobic cavity for ligand binding [23, 24]. Similar to other nsLTPs, Tri a 14 is a stable protein, not affected by heating up to 70°C, partially denatured at 90°C but losing up to 73% of its secondary structure after heating at 100°C, and resistant to proteolysis, retaining IgE-binding ability after experimental physico-chemical treatment in a fashion similar to that observed with Pru p 3 under the same conditions [8, 23]. However, IgE binding to Tri a 14 from cooked as compared to raw wheat albumin/globulin fraction may be abolished in a minority of wheat-allergic patients [8]. Other cereal LTPs, e.g. from maize, reportedly exhibit greater resistance to physico-chemical denaturation than Tri a 14 [8]. Known ligands of Tri a 14 are fatty acids, such as palmitic acid and linoleinic acid [24].
As of April 28, 2022, two isoallergens, Tri a 14.0101 and Tri a 14.0201, have been included in the World Health Organization (WHO) and International Union of Immunological Societies (IUIS) Allergen Nomenclature [2]. There is a 43.5% sequence identity between Tri a 14.0101, a 9.1 kDa nsLTP, and Tri a 14.0201, a 9.7 kDa nsLTP [11].
Tri a 14 shares moderate sequence identity with other nsLTPs, e.g. 45% between Tri a 14.0101 and Pru p 3, while Tri a 14.0201 exhibits higher sequence identity, at 47-49%, not only with Pru p 3 but also with Mal d 3 (Malus domestica, apple) [7, 11]. Tri a 14 displays both common and different epitopes when compared to Pru p 3, supporting moderate cross-reactivity [7, 10].
The demonstration of Tri a 14 sensitization is useful for the diagnosis of occupational and food-induced wheat allergy [3, 16]. Taking into account the 68-72% prevalence of clinically silent Tri a 14 sensitization, its demonstration in food-induced wheat allergy should be an incentive for applying an oral food challenge test in order to avoid unnecessary exclusion regimens [16].
The main route of exposure to Tri a 14 is through wheat ingestion. Occupational exposure to Tri a 14 in inhaled wheat flour may result in baker’s asthma. Finally, a nsLTP syndrome may result in cross-reactivity to Tri a 14.
Author: Joana Vitte
Reviewer: Dr.Christian Fischer
Last reviewed: June 2022