rCor a 14, Hazelnut

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Code: f439
Latin name: Corylus avellana
Source material: rCor a 14 is a CCD-free recombinant protein
Family: Betulaceae
Common names: 2S Albumin

ImmunoCAP allergen components:

rCor a 1
rCor a 8
nCor a 9
rCor a 14

Allergen: Cor a 14 (1, 2). rCor a 14 is a CCD-free recombinant protein.

Biological function: A 2S albumin

Mw: Approximately 13-14 kDa 

Clinical Utility

Evidence that sensitization to Cor a 14 is associated with severe hazelnut allergy both in children and adults have been reported (1, 2).

Recombinant and natural 2S albumin from hazelnut have been shown to have similar IgE reactivity (1). Of 36 patients recruited based on reported moderate to severe allergic reactions to nuts, sometimes specified as hazelnuts, and tested against the recombinant 2S albumin, 11 sera showed IgE-reactivity >0.35 kUA/L. Of the 11 patients, 8 reported a history suggestive of hazelnut allergy, including 5 with reported severe symptoms (1).

Allergen Exposure

See Hazelnut, f14

Allergen Description

Cor a 14 is a pollen-independent hazelnut allergen.

Cor a 14 is a 13-14 kDa protein, a 2S albumin protein. Cor a 14 is an abundant seed storage protein in hazelnut.  2S albumins are major seed storage proteins found in a variety of seeds and nuts including cottonseed, sunflower seed, castor bean, mustard, sesame, Brazil nut, walnut, cashew nut and peanut (3-5).  They are considered major allergens in peanut, walnut, Brazil nut, oilseed rape, castor bean, and mustard seed (5).

2S albumins are water-soluble seed storage proteins present in dicotyledonous plants, including legumes. Typical 2S albumins are small globular proteins rich in arginine, glutamine, asparagine, and often cysteine. They are typically heterodimers composed of a large and small subunit joined by one or two disulfide bridges that undergo proteolytic processing in the vacuoles of the plant cells, whereby the full-length precursor protein is usually cleaved into large and small subunits that stay associated through 2 disulphide bonds (4, 6). The characteristic of 2S albumin in other plant species is that the larger pre-albumin (14 kDa) is expressed along with the large (10-12 kDa) and small (5 kDa) subunits of the mature protein (7). For example, in Brazil nuts the precursor protein is 15 kDa, but the mature 2S albumin obtained from nut extract is 13 kDa (4).

2S albumins are considered to sensitize directly via the gastrointestinal tract; the high stability of their intrinsic protein structure despite the harsh conditions present in the GIT suggests that these proteins are able to cross the gut mucosal barrier to sensitize the mucosal immune system and/or elicit an allergic response (5).

Potential Cross-Reactivity

The cross-reactivity of Cor a 14 has not yet been evaluated, although a small study on cross-reactivity of heat stable proteins in walnut, hazelnut and Brazil nut was conducted, showing cross-reactivity between walnut and hazelnut heat stable  proteins (8). The homology between 2S albumins is generally rather low.

Clinical Experience

The prevalence of sensitization to Cor a 14 has been shown to differ between age groups: 70% of children and 39% of adults with hazelnut allergy with objective symptoms were rCor a 14 sensitized (2).

A study assessing the sensitization to the components rCor a 1, rCor a 8, nCor a 9, and rCor a 14 in a population of hazelnut-sensitized children and adults from a birch-endemic area concluded that sensitization to Cor a 9 and Cor a 14 was highly specific for patients with objective symptoms in double-blind, placebo-controlled food challenges (DBPCFCs) as a marker for a more severe hazelnut allergic phenotype. A group of 161 hazelnut-sensitized patients was included in the study: 40 children and 15 adults with objective symptoms on DBPCFCs, and 24 adults with a convincing objective history, were compared with 41 children and 41 adults with no or subjective symptoms on DBPCFCs (grouped together). IgE levels to hazelnut extract were significantly higher in children with objective than with no or with subjective symptoms. In 13% of children and 49% of adults with hazelnut allergy with objective symptoms, sensitization to only rCor a 1.04 was observed, not to other water-soluble allergens. Sensitization to rCor a 8 was rare, in contrast to rCor a 1. Sensitization to nCor a 9, rCor a 14, or both was strongly associated with hazelnut allergy with objective symptoms. IgE levels to either nCor a 9 of 1 kUA/L or greater or rCor a 14 of 5 kUA/L or greater (children) and IgE levels to either nCor a 9 of 1 kUA/L or greater or rCor a 14 of 1 kUA/L or greater (adults) had a specificity of greater than 90% and accounted for 83% of children and 44% of adults with hazelnut allergy with objective symptoms (2). Both children and adults without birch pollinosis had significantly higher IgE levels to nCor a 9 than those with birch pollen allergy. Levels of IgE to rCor a 14 were also higher in adults without than those with a history of allergic symptoms to birch pollen allergy, and no such difference was observed for IgE to rCor a 14 among children. IgE to nCor a 9 had better capacity than IgE to rCor a 14 to identify children with objective symptoms in DBPCFCs (2).

A strong correlation between IgE-binding to 2S albumins and food-induced anaphylaxis has been demonstrated for Brazil nut and sesame seeds (3). The role of the hazelnut 2S albumin, Cor a 14, needs to be fully elucidated.

See Hazelnut f17 for clinical information and further details on Hazelnut allergy.

Compiled by Dr Harris Steinman
harris@allergyadvisor.com

References

  1. Garino C, Zuidmeer L, Marsh J, Lovegrove A, Morati M, Versteeg S, Schilte P, Shewry P, Arlorio M, van Ree R. Isolation, cloning, and characterization of the 2S albumin: a new allergen from hazelnut. Mol Nutr Food Res 2010;54(9):1257-65.
  2. Masthoff LJ, Mattsson L, Zuidmeer-Jongejan L, Lidholm J, Andersson K, Akkerdaas JH, Versteeg SA, Garino C, Meijer Y, Kentie P, Versluis A, den Hartog Jager CF, Bruijnzeel-Koomen CA, Knulst AC, van Ree R, van Hoffen E, Pasmans SG. Sensitization to Cor a 9 and Cor a 14 is highly specific for a hazelnut allergy with objective symptoms in Dutch children and adults. J Allergy Clin Immunol 2013;132(2):393-9.
  3. Pastorello EA, Pompei C, Pravettoni V, Brenna O, Farioli L, Trambaioli C, Conti A. Lipid transfer proteins and 2S albumins as allergens. Allergy 2001;56(S67):45-7.
  4. Robotham JM, Wang F, Seamon V, Teuber SS, Sathe SK, Sampson HA, Beyer K, Seavy M, Roux KH. Ana o 3, an important cashew nut (Anacardium occidentale L.) allergen of the 2S albumin family. J Allergy Clin Immunol 2005;115(6):1284-90.
  5. Moreno FJ, Clemente A. 2S Albumin storage proteins: what makes them food allergens? Open Biochem J 2008;2:16-28.
  6. Teuber SS, Dandekar AM, Peterson WR, Sellers CL. Cloning and sequencing of a gene encoding a 2S albumin seed storage protein precursor from English walnut (Juglans regia), a major food allergen. J Allergy Clin Immunol 1998;101(6 Pt 1):807-14.
  7. Roux KH, Teuber SS, Sathe SK. Tree nut allergens. Int Arch Allergy Immunol 2003;131(4):234-44.
  8. Asero R, Mistrello G, Roncarolo D, Amato S. Walnut-induced anaphylaxis with cross-reactivity to hazelnut and Brazil nut. J Allergy Clin Immunol. 2004 Feb;113(2):358-60.

 

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.