Component-resolved diagnostics (CRD), how to read the result
Maps the commonly ordered allergen components onto their protein family, their stability to heat and digestion, and what a positive result actually predicts. Stable families (storage proteins, lipid transfer proteins) carry systemic-reaction risk; labile families (PR-10, profilin) usually mean oral symptoms only.
Evidence tier: Guideline-derived.
| Component | Protein family & stability | What a positive result means |
|---|---|---|
| Ara h 2 and Ara h 6 (peanut) | 2S albumin storage protein. Stable to heat and digestion. | The most useful single serologic marker for genuine peanut allergy. Positivity predicts systemic reaction risk far better than whole peanut sIgE, which is frequently positive on cross-reactivity alone. Ara h 6 tracks closely with Ara h 2. Ara h 1 and Ara h 3 (7S/11S globulins) are also storage proteins and carry the same implication when positive. |
| Ara h 8 (peanut) | PR-10 / Bet v 1 homologue. Destroyed by heat and digestion. | Usually reflects birch pollen cross-reactivity rather than true peanut allergy. The typical clinical picture is oral allergy syndrome with raw peanut and tolerance of roasted. An ISOLATED Ara h 8 positive with negative storage proteins argues against systemic peanut allergy, this is the single most common CRD pattern that prevents an unnecessary lifelong avoidance label. |
| Cor a 14 (hazelnut), Jug r 1 (walnut), Ana o 3 (cashew), Ses i 1 (sesame), Gly m 8 (soy) | 2S albumin storage proteins. Stable. | The tree-nut, sesame and soy analogues of Ara h 2. A positive result supports genuine, potentially systemic allergy to that food. Cor a 1 and Cor a 2 (hazelnut PR-10 and profilin) carry the opposite implication and usually indicate pollen cross-reactivity. |
| Pru p 3 (peach) and its homologues, Ara h 9, Cor a 8, Jug r 3, Tri a 14 | Non-specific lipid transfer protein (nsLTP). Stable to heat, digestion and processing. | Systemic-reaction risk, and the dominant food-allergy pattern in Mediterranean populations where it often eclipses pollen-driven allergy. LTP reactions are frequently COFACTOR-dependent (exercise, NSAIDs, alcohol), so a patient can tolerate the food at rest and react to the same food with a cofactor, do not clear them on a resting challenge alone. |
| Bet v 1 homologues, Mal d 1 (apple), Pru p 1 (peach), Cor a 1 (hazelnut), Gly m 4 (soy) | PR-10. Labile to heat and digestion. | Birch-pollen-driven cross-reactivity: oral itch and tingling with the raw food, usually tolerated cooked. IMPORTANT EXCEPTION: Gly m 4 can cause systemic reactions, particularly to soy beverages and soy protein supplements, so a positive Gly m 4 should not be dismissed as merely oral. |
| Profilins, Bet v 2, Ara h 5, Cor a 2, Pru p 4 | Profilin. Highly labile; pan-allergen across pollens, fruits and vegetables. | Usually clinically irrelevant on its own. Its main practical role is explaining widespread, confusing multi-food sIgE positivity in a patient who eats those foods without difficulty. Treat as cross-reactivity noise unless the history genuinely fits. |
| Tri a 19 (omega-5 gliadin, wheat) | Gliadin storage protein. Stable. | The marker for wheat-dependent exercise-induced anaphylaxis. Routine wheat SPT and whole-wheat sIgE are frequently NEGATIVE in WDEIA, so this component is what makes the diagnosis in a patient who reacts to wheat only alongside exercise, NSAIDs or alcohol. |
| Gal d 1 (ovomucoid) vs Gal d 2 (ovalbumin), egg | Gal d 1 is heat-stable; Gal d 2 is heat-labile. | The baked-egg question. Gal d 1 positivity predicts reaction to BAKED egg and a more persistent allergy; a low or negative Gal d 1 with positive Gal d 2 raises the possibility of baked-egg tolerance. It informs, but does not replace, a supervised baked-egg challenge. |
| Bos d 8 (casein) vs Bos d 4 / Bos d 5 (whey), milk | Casein is heat-stable; alpha-lactalbumin and beta-lactoglobulin are more labile. | The baked-milk counterpart. High casein predicts reaction to baked milk and a more persistent course; whey-predominant sensitisation is more compatible with baked-milk tolerance. Again informative, not a substitute for a supervised challenge. |
| Alpha-gal (galactose-alpha-1,3-galactose) | Oligosaccharide, not a protein. Present in non-primate mammalian tissue. | Delayed (typically 3-6 hour) reactions to mammalian meat after tick bite sensitisation, and immediate reactions to cetuximab. The delay and the absence of a mealtime-proximate trigger are why this is missed; suspect it in adult-onset "idiopathic" anaphylaxis. |
| CCD, cross-reactive carbohydrate determinants (e.g. MUXF3) | Carbohydrate epitope shared across plant and insect glycoproteins. | Clinically IRRELEVANT in almost all cases, but a common cause of false-positive extract-based sIgE across many unrelated plant foods and venoms. A CCD-positive patient with broad, clinically silent positivity is the classic reason to move to component testing. Also the reason venom testing can appear dual-positive to both honeybee and vespid. |
| Api m 1 (honeybee) and Ves v 5 / Ves v 1 (vespid) | Species-specific venom proteins, free of CCD interference. | Used to resolve apparent DUAL positivity to bee and wasp on whole-venom testing, which is usually CCD cross-reactivity rather than true double sensitisation. Identifying the genuine culprit determines which venom immunotherapy the patient receives, a decision with years of treatment behind it. |
Notes
- CRD does NOT replace the oral food challenge. The challenge remains the diagnostic reference standard; components refine probability and risk, they do not settle the diagnosis.
- Order components to answer a QUESTION raised by history and extract testing, most often to resolve discordance or to explain broad positivity. Ordering a component panel as a screen reproduces the same over-diagnosis problem as ordering broad extract panels.
- The single most useful organising principle: heat- and digestion-STABLE families (2S albumins and other storage proteins, nsLTP) associate with systemic reactions, while LABILE families (PR-10, profilin) associate with oral symptoms and tolerance of the cooked food.
- A negative component does not exclude allergy. Component panels are not exhaustive, sensitisation can be to an untested protein, and assay performance varies by platform.
- Sensitisation is not allergy. A positive component in a patient who eats the food without symptoms is not a reason to start avoidance.
- Cofactor-dependent presentations (LTP and omega-5 gliadin in particular) can pass a resting oral food challenge. If the history is cofactor-linked, a negative resting challenge does not clear the patient.
Evidence & citations
- Santos AF, Riggioni C, Agache I, et al. EAACI guidelines on the diagnosis of IgE-mediated food allergy. Allergy. 2023;78(12):3057-3076. PMID 37815205
- Riggioni C, Ricci C, Moya B, et al. Systematic review and meta-analyses on the accuracy of diagnostic tests for IgE-mediated food allergy. Allergy. 2024;79(2):324-352. PMID 38009299
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