Total IgE

Immunoglobulin E (IgE) is the least abundant immunoglobulin (under 0.001% of total immunoglobulin) and mediates immediate hypersensitivity through binding to high affinity receptors on mast cells and basophils. Total serum IgE is measured by fluoroimmunoassay, chemiluminescence or nephelometry (kU/L or IU/mL; 1 IU equals 2.4 ng).

It is raised in atopic disease, parasitic infection, allergic bronchopulmonary aspergillosis, hyper-IgE syndromes, some immunodeficiencies and some malignancies. It is a non-specific marker, and a normal value does not exclude allergy, since allergen specific IgE may be present with a normal total.

Atopy affects 20 to 30% of people in high income countries, and total IgE is raised in about 40 to 60% of atopic patients but also in 10 to 20% of non-atopic people. Its principal clinical uses are: to support the diagnosis of allergic bronchopulmonary aspergillosis in asthma (total IgE over 1000 IU/mL), to select and dose patients for omalizumab in severe asthma, to evaluate suspected hyper-IgE syndrome, and as a pointer to helminth infection.

Indications. Severe or poorly controlled asthma (before omalizumab, to dose it with body weight). Suspected allergic bronchopulmonary aspergillosis (asthma, fleeting infiltrates, central bronchiectasis, eosinophilia). Atopic dermatitis with recurrent infections and abscesses (hyper-IgE syndrome). Unexplained eosinophilia (parasites, drug reaction, Churg-Strauss syndrome). Chronic urticaria evaluation in some centres. Not for diagnosing food or drug allergy.

Specimen. Serum 1 mL, no fasting. Stable for several days at 2 to 8 °C. The sample is not affected by season, but is affected by recent allergen exposure.

Reference ranges (age dependent, assay dependent).

Interpretation.

• Mildly raised (100 to 500 kU/L): atopy (allergic rhinitis, asthma, eczema), smoking, and many non-allergic conditions.
• Markedly raised (500 to 1000 kU/L): severe atopic dermatitis, allergic bronchopulmonary aspergillosis, helminth infection, drug reaction.
• Very high (over 1000 kU/L): allergic bronchopulmonary aspergillosis (threshold over 1000 IU/mL, or over 500 in some criteria), hyper-IgE syndrome (usually over 2000 kU/L), Wiskott-Aldrich syndrome, Omenn syndrome, IgE myeloma (rare), severe atopic dermatitis.
• Normal: does not exclude allergy, and specific IgE or skin testing are needed.
• Low IgE (under 2 kU/L): not clinically useful, but seen in agammaglobulinaemia and ataxia telangiectasia.

Specific conditions.

• Allergic bronchopulmonary aspergillosis: total IgE over 1000 IU/mL (a normal total IgE makes it unlikely), raised Aspergillus specific IgE or IgG, positive skin test, and eosinophilia. A fall of 35 to 50% after treatment indicates response, and a rise over 100% suggests relapse.
• Hyper-IgE syndrome (STAT3 deficiency, Job syndrome): IgE over 2000 kU/L, eczema, recurrent staphylococcal skin abscesses, pneumonia with pneumatoceles, coarse facies, retained primary teeth and fractures. Scores such as the NIH hyper-IgE score are used.
• Helminth infection: raised IgE with eosinophilia (strongyloidiasis, ascariasis, schistosomiasis, filariasis, toxocariasis, hookworm).
• Omalizumab dosing: dose and interval are based on baseline total IgE (30 to 1500 IU/mL) and body weight (30 to 150 kg), and total IgE rises after starting treatment (bound IgE), so it is not used to monitor.
• Other raised IgE: eosinophilic oesophagitis and granulomatosis with polyangiitis, Kimura disease, HIV, bullous pemphigoid, graft-versus-host disease, Hodgkin lymphoma and drug reactions.

Critical values and findings needing immediate action.

• Total IgE over 1000 IU/mL with asthma and central bronchiectasis: allergic bronchopulmonary aspergillosis, treatment with oral corticosteroids and antifungal drugs to prevent bronchiectasis and fibrosis.
• Very high IgE in an infant with severe eczema, infections and failure to thrive: primary immunodeficiency (hyper-IgE, Wiskott-Aldrich, Omenn), urgent immunology referral.
• Raised IgE with eosinophilia, rash, fever and organ involvement: drug reaction with eosinophilia and systemic symptoms, stop the offending drug.
• Raised IgE and eosinophilia in a migrant or traveller: strongyloidiasis screening before immunosuppression (risk of hyperinfection).

Interferences and pitfalls.

• Total IgE is neither sensitive nor specific for allergy. Allergic disease is diagnosed from history, skin prick tests or specific IgE, not from total IgE.
• Reference ranges depend on age, sex (higher in men), ethnicity and geography, and in tropical countries helminth infections raise baseline IgE.
• Smoking, exposure to cigarette smoke and cannabis raise IgE.
• Very high IgE can saturate some assays and produce falsely low values (hook effect), so dilution is used.
• Anti-IgE therapy (omalizumab) raises total IgE as it binds drug complexed IgE, and the test cannot direct treatment response.
• Monoclonal IgE and other paraproteins (IgE myeloma) require electrophoresis.
• Measurement during acute allergic reactions is not helpful (serum tryptase is the marker for anaphylaxis).
• A normal IgE with typical symptoms does not rule out atopy, and component resolved diagnostics refine risk.

Special groups.

• Infants: cord blood IgE is low, and early high levels predict atopic disease risk, though poorly.
• Children: values rise in school years and peak in adolescence, and age specific percentiles are used.
• Pregnancy: no significant change.
• Older adults: levels fall with age.
• Regions: high levels are common in helminth endemic areas, and IgE alone does not settle allergy diagnosis there.

Follow up tests. Allergen specific IgE panels and skin prick tests, full blood count with eosinophil count, Aspergillus fumigatus specific IgE and IgG, sputum eosinophils, chest radiograph and CT, spirometry with reversibility, FeNO, stool microscopy and Strongyloides serology, serum tryptase, STAT3 gene analysis and lymphocyte phenotyping in suspected hyper-IgE syndrome, and serum protein electrophoresis.