Immunological differences between insect venom‐allergic patients with and without immunotherapy and asymptomatically sensitized subjects

• Published in: Allergy (Copenhagen) Vol. 73; no. 6; pp. 1223 - 1231
• Main Authors: Arzt, L., Bokanovic, D., Schrautzer, C., Laipold, K., Möbs, C., Pfützner, W., Herzog, S. A., Vollmann, J., Reider, N., Bohle, B., Aberer, W., Sturm, G. J.
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.06.2018
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Allergens; Allergens - immunology; Allergies; Antibody Specificity - immunology; Arthropod Venoms - immunology; Asymptomatic Diseases; basophil activation test; Bees; Biological Variation, Population; Female; Humans; hymenoptera venom allergy; Hypersensitivity - diagnosis; Hypersensitivity - etiology; Hypersensitivity - therapy; IgE; IgG4; Immunoassay; Immunoglobulin E; Immunoglobulin E - blood; Immunoglobulin E - immunology; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunological tolerance; Immunology; Immunotherapy; Insect Bites and Stings - complications; Insect Bites and Stings - immunology; Male; Middle Aged; Phenotype; Sensitivity and Specificity; Stings; Venom; venom immunotherapy; Young Adult; IgG4; basophil activation test; hymenoptera venom allergy; venom immunotherapy; IgE
• ISSN: 0105-4538; 1398-9995; 1398-9995
• DOI: 10.1111/all.13368

Background Currently available tests are unable to distinguish between asymptomatic sensitization and clinically relevant Hymenoptera venom allergy. A reliable serological marker to monitor venom immunotherapy (VIT) does also not exist. Our aim was to find reliable serological markers to predict tolerance to bee and vespid stings. Methods We included 77 asymptomatically sensitized subjects, 85 allergic patients with acute systemic sting reactions, and 61 allergic patients currently treated with VIT. Levels of sIgE and sIgG4 to bee and vespid venom, rApi m 1, and rVes v 5 were measured immediately after allergic sting reactions or before sting challenges and 4 weeks later. All sting challenges were tolerated. The inhibitory activity was determined using BAT inhibition and ELIFAB assay. Results Median sIgG4 levels were 96‐fold higher in VIT patients (P < .001) while sIgE/sIgG4 ratios were consistently lower (P < .001). The ELIFAB assay was paralleled by low sIgE/sIgG4 ratios in VIT patients, showing markedly higher allergen‐blocking capacity (P < .001). An almost complete inhibition of the basophil response was seen in all patients treated with vespid venom, but not in those treated with bee venom. Four weeks after the sting, sIgE and sIgG4 levels were increased in allergic and asymptomatically sensitized patients, but not in VIT patients. Conclusion Immunological responses after stings varied in bee and vespid venom‐allergic patients. In patients under VIT, sIgE and sIgG4 remained completely stable after sting challenges. Monitoring VIT efficacy was only possible in vespid venom allergy, and the sIgG4 threshold for rVes v 5 had the highest sensitivity to confirm tolerance. The BAT inhibition test was the most reliable tool to confirm tolerance on an individual basis.