ImmunoCAP ISAC — Component-Resolved Diagnosis

Standard sIgE assays and skin prick testing detect sensitisation to whole allergen extracts — mixtures of many proteins. They cannot easily distinguish between sensitisation to a clinically relevant primary protein and sensitisation to a cross-reactive epitope shared across multiple, unrelated allergen sources.

Component-resolved diagnosis (CRD) identifies the specific molecular component driving the sIgE response, which can change clinical interpretation. Two illustrative patterns commonly cited in the literature:

• Peanut: sIgE to Ara h 2 (and Ara h 1, 3, 6) — storage proteins — is strongly associated with systemic reactions. sIgE to Ara h 8 alone (a PR-10 homologue of Bet v 1) is typically associated with pollen-food syndrome with mild oral symptoms.
• Cross-reactive carbohydrate determinants (CCDs): non-allergenic glycan epitopes that produce widespread positive results in conventional testing without clinical relevance. CRD identifies these and prevents over-diagnosis.
• nsLTPs (Pru p 3 and similar): heat- and digestion-stable, associated with systemic reactions to a range of plant foods.

CRD therefore changes management in selected scenarios: risk stratification, avoidance counselling, immunotherapy candidate selection.

Reasonable clinical scenarios where ISAC (or targeted single-component sIgE) may add value, generally via immunologist:

• Inconsistent history vs results: standard testing positive but clinical reactions don't match the suspected trigger.
• Polysensitised patient: multiple positive sIgE / SPT results, unclear which is clinically relevant.
• Idiopathic anaphylaxis: recurrent anaphylaxis without identifiable trigger; CRD may detect occult sensitisation (e.g. nsLTP, α-gal, ω-5 gliadin in WDEIA).
• Allergen immunotherapy planning: distinguish primary sensitisation from cross-reactivity to choose the correct extract.
• Venom double-positivity: bee and wasp both positive — Api m 1 vs Ves v 5 / v 1 distinguishes true double sensitisation from cross-reactivity, guiding venom immunotherapy.
• Food allergy in atopic patients: when pollen-food syndrome is suspected vs primary food allergy.

Not appropriate as: general allergy screen, replacement for clinical history, first-line investigation in straightforward single-allergen disease (e.g. clear seasonal rhinitis, confirmed isolated food allergy that's well managed).

• Results reported in ISU-E (ISAC Standardised Units) per component, banded low / moderate / high / very high.
• A positive IgE is sensitisation, not clinical allergy. Match to history.
• ISAC is generally less sensitive than singleplex ImmunoCAP for any given allergen. A negative ISAC for a component does not exclude allergy if clinical suspicion is high — confirm with targeted singleplex sIgE.
• Fixed 112-component panel — clinically relevant allergens may be absent. Read the panel composition before ordering.
• Multiple positives are common, especially in atopic patients; interpretation needs an immunologist familiar with cross-reactive component patterns.
• Results are useful for risk-stratification and counselling; they do not replace oral food challenge as the gold standard for confirming food allergy.

ImmunoCAP ISAC: No MBS item. Private fee, typically A$300–600. Some private health insurance extras cover part of the cost; not all laboratories offer the test (specialised allergy laboratories only).

Targeted single-component sIgE (e.g. Ara h 2, Pru p 3): may be available through some laboratories and may attract a private fee. Discuss with the immunologist before requesting.

Standard single-allergen sIgE (whole extract): MBS items 71089–71092, subject to limits (currently up to four allergens per request, with annual frequency caps). Verify the current item details on MBS Online.

Referral pathway: for complex allergy where CRD is being considered, refer to a clinical immunologist (FRACP allergy/immunology). The immunologist arranges the test, interprets the result in clinical context, and feeds back to the GP for ongoing care.

Child with seasonal rhinitis and tingling lips after apple, kiwi, hazelnut. SPT positive to birch and several stone fruits. Standard panel may suggest a wide range of food allergies. CRD typically shows positive sIgE to PR-10 components (Bet v 1, Mal d 1, Pru p 1, Cor a 1) and negative to nsLTPs (Pru p 3) and storage proteins. This pattern supports pollen-food syndrome (oral allergy syndrome) — heat- and digestion-labile, low risk of systemic reaction, no strict avoidance needed (cooked fruit usually tolerated). Avoidance and adrenaline are not first-line; reassurance and patient education are. Decision rests with the treating immunologist.

Recurrent anaphylaxis without obvious food, drug, or insect trigger. Targeted ω-5 gliadin (Tri a 19) sIgE may identify wheat-dependent exercise-induced anaphylaxis (WDEIA); Pru p 3 may identify nsLTP-driven food anaphylaxis; α-gal (alpha-Gal IgE) identifies mammalian meat allergy (also test for tick exposure). ISAC includes several of these components, so it can be a useful screen in this scenario. Galactose-α-1,3-galactose alpha-gal alone may not be on every panel — verify with the laboratory and consider targeted singleplex if needed. Source: ASCIA; clinical literature.