Multiplex IgE reactivity without a documented corresponding phenotype: cross-sectional patterns and routine-care follow-up
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Authors Information
1Fondazione Luigi Maria Monti, IDI-IRCCS, Rome, Italy
2Allergy and Clinical Immunology Unit, San Giovanni di Dio Hospital, Florence, Italy
3Laboratory Immunology and Allergology Unit, S. Maria degli Angeli Hospital, Pordenone, Italy
4Allergy Outpatient Clinic, Clinica San Carlo, Paderno Dugnano, Milan, Italy
History
Published: 19 October 2026
Accepted: 04 October 2026
Received: 30 July 2026
SUMMARY
Background. Multiplex diagnostics may identify IgE reactivity without a corresponding phenotype documented at testing. This record-level discordance can reflect incomplete history, limited exposure, cross-recognition, or broader atopy and is not equivalent to asymptomatic sensitisation. We described concordance across six allergen groups and routine-care reassessment of selected Pru p 3/nsLTP and Hymenoptera findings. Methods. We retrospectively analyzed ALEX2 assessments, retaining one index-positive test per patient and allergen group. Pairs were classified according to whether a compatible phenotype was documented at index assessment. Follow-up of selected Pru p 3/nsLTP and Hymenoptera findings were non-standardized, descriptive, and restricted to patients retained in routine care by July 2026. Results. Among 3,636 patients, 1,241 were positive to at least one group, yielding 1,698 pairs: 667 (39.3%) had a documented corresponding phenotype and 1,031 (60.7%) did not. Atopic dermatitis did not increase record-level discordance compared with respiratory atopy without atopic dermatitis. Among 316 Pru p 3-positive patients without a documented phenotype, 290 were retained; 219 reported a compatible post-index reaction after plant-food exposure and 71 did not, including 55 with documented tolerance. Among 204 Hymenoptera-reactive patients without a documented sting phenotype, 112 were retained; 31 reported a post-index sting-associated event and 81 reported no post-index sting. Conclusions. In this tertiary-care cohort, absence of a documented corresponding phenotype was frequent. Routine-care reassessment yielded heterogeneous exposure-based outcomes but cannot estimate asymptomatic sensitisation, clinical penetrance, or future risk. The findings support clinical verification rather than automatic dismissal or allergy labelling.






