A systematic review of total IgE reference intervals - A 2024 update

Total IgE (tIgE) is a frequently requested analyte in patients presenting with symptoms of atopy. Although tIgE has limited clinical utility in the diagnosis of atopic diseases, it is still important that appropriate reference intervals are provided to the intepreting clinician. Concerns have recently been raised whether laboratories may be using outdated tIgE reference intervals. The aim of this study was therefore to perform the first systematic literature review of tIgE reference intervals to aid laboratories in choosing appropriate sources.

A search was performed in MEDLINE, Embase and the Cochrane Library from time of inception to July 2024. Eligible studies had to provide an estimate of paediatric and/or adult tIgE reference intervals using current generation immunoassays. The methodology followed PRISMA guidelines, and the study protocol was registered in the PROSPERO database (CRD42023396441).

A total of 1667 records were screened of which 20 studies remained after full text review. The studies included 23 910 individuals and covered 18 countries. Upper reference limits varied significantly, with participant selection (inclusion or exclusion of in vitro confirmed specific IgE sensitised individuals) and statistical methods identified as the most important factors influencing the upper reference limit.

This review emphasises the need for laboratories to carefully evaluate the participant selection criteria and employed statistical methods whilst determining which tIgE reference intervals are the most appropriate to report to clinicians. Further efforts must also be made to harmonise and improve the reporting of tIgE reference interval studies.