Jug r 2
Allergen
Summary
Jug r 2 is a 7S globulin (vicilin) seed storage protein from English walnut (Juglans regia). It is a member of the cupin superfamily and notable for its heat and proteolytic stability. Jug r 2 acts as a primary sensitizing walnut allergen and a marker of genuine walnut allergy rather than pollen-related cross-reactivity. Sensitization to Jug r 2 is associated with systemic, often severe reactions, including anaphylaxis, and is especially relevant in patients with early-onset walnut allergy.
Epidemiology
Walnut is among the most clinically relevant causes of tree nut allergies worldwide. According to data from the EuroPrevall project, 3% of the adult European population is predicted to be sensitized to walnut, ranging from 0.1% in Iceland to 6% and 8% in Switzerland and Spain, respectively. Sensitization to walnut among children across Europe ranges from 1.4% in Iceland to 9.5% in Switzerland.
In a systematic review and meta-analysis, walnut allergy and sensitization were assessed in 12 studies, of which 11 contributed data to the pooled sensitization analyses. Across these studies, the prevalence of walnut specific IgE sensitization was 4.1% and 2.7% for skin prick testing. In contrast, the pooled estimate for food challenge–confirmed walnut allergy was 0.02%, based on one available study.
According to telephone interviews with 4,855 randomly selected households in the United States, 62% of participants (51/82) who had information about their specific tree nut allergies, reported having walnut allergy.
Data from the European Anaphylaxis Registry, collected between 2007 and 2015, showed that among children and adolescents with anaphylaxis to tree nuts, walnuts were one of the most significant triggers, accounting for 16% (42/256) of the cases.
Sensitization to Jug r 2 and other walnut storage proteins is associated with early-onset walnut allergy in childhood and correlates with severe reactions.
In Ballmer-Weber et al. (2019), vicilin sensitization (Jug r 2 and Jug r 6) was consistently frequent across all European regions studied (Switzerland, Germany, Spain). Unlike other allergens with regionally skewed patterns—such as Jug r 3 (nsLTP), dominant in Spain, or Jug r 5 (PR-10), dominant in birch-endemic central Europe—the vicilin allergens Jug r 2/Jug r 6 showed no strong regional variation. This indicates that Jug r 2 and Jug r 6 act as primary sensitizers across regions with different climates and pollen exposure.
Route Of Exposure
Exposure occurs through ingestion of raw, roasted, or processed walnut products. Jug r 2 is thermostable and resists degradation during cooking or digestion, explaining reactions to trace amounts of walnut vicilins in baked or confectionery goods.
Clinical Relevance
Jug r 2 is a clinically important allergen linked to severe systemic reactions, including anaphylaxis. In a prospective multicentre study of 115 European patients assessing walnut allergy severity and component resolved sensitization across age groups and regions, vicilin fractions containing Jug r 2 and Jug r 6 fragments correlated significantly with severe symptoms in children. The same study also reported that sensitization to those vicilin fractions is closely associated with early-onset of walnut allergy.
The prevalence of Jug r 2 sensitization varies dependent on patient population. Early work by Teuber (1999) identified Jug r 2 as a major allergen, with IgE recognition in 60% (9/15) of patients from USA with severe systemic walnut allergy. In contrast, among an Italian cohort predominantly characterised by LTP-driven allergy, vicilin sensitization was detected in 22% (10/46) of patients. Similarly, in a small group UK/Spain cohort with confirmed history of walnut allergy, 27% (3/11) showed IgE-reactivity to 7S globulin fragments.
Small amounts of walnut can trigger severe reactions in patients’ monosensitized to Jug r 2 as illustrated by a recent case report. The patient experienced anaphylaxis within 30 mins after ingestion of a salad from which a walnut topping had been removed. Walnut extract IgE was 4.98 kUA/l and component testing showed Jug r 2–specific IgE of 8.58 kUA/L. Specific IgE was <0.10 kUA/L for Jug r 1, Jug r 3, Jug r 6, and 0.29 kUA/L for Jug r 4.
Diagnostics
Component-resolved diagnosis using Jug r 2 can improve discrimination between primary walnut allergy and birch pollen–related cross-reactivity. Specific IgE to Jug r 2 also appears to be a useful marker for identifying patients at increased risk of severe reactions. In addition, Jug r 2 sensitization is associated with early-onset walnut allergy, with significantly higher sensitization rates in patients whose symptoms began in childhood (<14 years), providing valuable clinical information in the context of paediatric and early-onset disease.
Prevention And Therapy
There is currently no regulatory approved walnut oral immunotherapy available. Management involves avoidance of walnut and often cross-reactive nuts (especially pecan), education and epinephrine auto-injector prescription when indicated.
In a clinical study including 73 walnut allergic patients it was demonstrated that walnut oral immunotherapy can induce desensitisation to walnut as well as cross-desensitisation to pecan and, in some cases, hazelnut in patients who have tree nut co-allergies.
Cross-Reactivity
Inhibition studies demonstrated that walnut pretreatment completely blocks IgE binding to pecan indicating presence of shared epitopes that could lead to 7S globulin-mediated walnut-pecan clinical cross-reactivity. Walnut oral immunotherapy can induce cross-desensitisation to pecan and hazelnut in patients who have tree nut co-allergies. IgE cross-reactivity between Jug r 2 and pecan 7S globulin Car i 2, is expected based on their close to 70% amino acid sequence identity and presumed high similarity of molecular structures.
Jug r 2 shares 44% amino acid identity with Jug r 6 vicilin and 30-70% identity with 7S globulins from other tree nuts, such as pecan (Car i 2), hazelnut (Cor a 11), pistachio (Pis v 3), and cashew (Ana o 1). It also shares identity with seeds, such as sesame (Ses i 3) and lupin (Lup an 1), and legumes, such as peanut (Ara h 1) and soybean (Gly m 5).
The cupin domains of Jug r 2 and Cor a 16 share 72% sequence identity (personal communication Jonas Lidholm) indicating a strong likelihood for IgE cross-reactivity.
Explained Results
Allergen information
Jug r 2 is a 7S globulin (vicilin) seed storage protein. It is heat- and digestion-stable and functions as a marker of genuine walnut allergy.
Clinical relevance
Jug r 2 sensitization is linked to severe systemic reactions and is closely associated with early-onset walnut allergy. Data suggests that Jug r 2 acts as a primary sensitizing walnut allergen across regions with climates and pollen exposure.
Cross-reactivity
Jug r 2 has close to 70% amino acid sequence identity with pecan vicilin Car i 2 that is expected to lead to clinical cross-reactivity. Jug r 2 also show around 40% identity with vicilins from other tree nuts, seeds and legumes.
References
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