Profound differences in IgE and IgG recognition of micro‐arrayed allergens in hyper‐IgE syndromes

Victoria Garib (1, 2) , Meriem Ben-Ali (3, 4) , Michael Kundi (1) , Mirela Curin (1) , Roukaya Yaakoubi (3, 4) , Imen Ben-Mustapha (3, 4) , Najla Mekki (3, 4) , Renate Froeschl (1) , Thomas Perkmann (1) , Rudolf Valenta (1, 5, 6, 7) , Mohamed-Ridha Barbouche (3, 4)

1 Medizinische Universität Wien = Medical University of Vienna
2 Ministry of innovative development of the Republic of Uzbekistan
3 LR11IPT02 - Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of Infection
4 UTM - Université de Tunis El Manar
5 NRC Institute of immunology FMBA
6 Sechenov First Moscow State Medical University
7 Karl Landsteiner University of Health Sciences - Karl Landsteiner Privatuniversität für Gesundheitswissenschaften [Krems an der Donau, Austria]

Background The specificities of IgE and IgG for allergen molecules in patients with inborn errors of immunity (IEI) have not been investigated in detail. Objective To study IgE and IgG antibody specificities in patients with defined hyper-IgE syndromes (HIES) using a comprehensive panel of allergen molecules. Methods We used chips containing micro-arrayed allergen molecules to analyze allergen-specific IgE and IgG levels in sera from two groups of HIES patients: Autosomal recessive mutations in phosphoglucomutase-3 (PGM3); Autosomal dominant negative mutations of STAT3 (STAT3); and age-matched subjects with allergic sensitizations. Assays with rat basophil leukemia cells transfected with human FcεRI were performed to study the biological relevance of IgE sensitizations. Results Median total IgE levels were significantly lower in the sensitized control group (212.9 kU/L) as compared to PGM3 (5042 kU/L) and STAT3 patients (2561 kU/L). However, PGM3 patients had significantly higher allergen-specific IgE levels and were sensitized to a larger number of allergen molecules as compared to STAT3 patients. Biological relevance of IgE sensitization was confirmed for PGM3 patients by basophil activation testing. PGM3 patients showed significantly lower cumulative allergen-specific IgG responses in particular to milk and egg allergens as compared to STAT3 patients and sensitized controls whereas total IgG levels were comparable to STAT3 patients and significantly higher than in controls. Conclusion The analysis with multiple micro-arrayed allergen molecules reveals profound differences of allergen-specific IgE and IgG recognition in PGM3 and STAT3 patients which may be useful for classification of IEI and clinical characterization of patients.

Mots clés: allergen; hyper-IgE syndrome (HIES); micro-array; phosphoglucomutase-3 (PGM3) deficiency; signal transducer and activator of transcription (STAT3)

Domaines: Sciences du Vivant [q-bio]

Victoria Garib, Meriem Ben-Ali, Michael Kundi, Mirela Curin, Roukaya Yaakoubi, et al.. Profound differences in IgE and IgG recognition of micro‐arrayed allergens in hyper‐IgE syndromes. Allergy, 2021, pp.Online Version of Record before inclusion in an issue. ⟨10.1111/all.15143⟩. ⟨pasteur-03545472⟩