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. 2022 Jun;77(6):1761-1771.
doi: 10.1111/all.15143. Epub 2021 Nov 2.

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

Victoria Garib  1   2 , Meriem Ben-Ali  3 , Michael Kundi  4 , Mirela Curin  1 , Roukaya Yaakoubi  3 , Imen Ben-Mustapha  3 , Najla Mekki  3 , Renate Froeschl  5 , Thomas Perkmann  5 , Rudolf Valenta  1   6   7   8 , Mohamed-Ridha Barbouche  3   9
Affiliations

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

Victoria Garib et al. Allergy. 2022 Jun.

Abstract

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.

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

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Conflict of interest statement

Rudolf Valenta has received research grants from Viravaxx, Vienna, Austria, HVD‐Biotech, Vienna, Austria and WORG Pharmaceuticals, Hangzhou, China. He serves as a consultant for Viravaxx. The other authors have no conflicts of interest to declare.

Figures

FIGURE 1
FIGURE 1
Comparison of A, total IgE, B, total IgG, C, cumulative allergen‐specific IgE, D, cumulative allergen‐specific IgG levels as well as of cumulative IgE levels E, and cumulative IgG levels, F, specific for cow´s milk and egg allergens (FA1), nut‐, seed‐, fruit‐, wheat‐, fish‐ and shrimp allergens (FA2), pollen allergens, HDM allergens (HDM), other respiratory allergens (other RA) and other allergens (OAs) in PGM3, STAT3 patients and allergic controls (x‐axes). y‐axes show total IgE kU/L; total IgG g/L; sum of specific IgE ISU, sum of specific IgG ISU on a log scale, bars represent geometric means with individual data points included and 95% confidence intervals are indicated. Significant differences were calculated for the cumulative allergen‐specific IgE levels. p values below 0.05 were considered significant and are indicated
FIGURE 2
FIGURE 2
Heat map of IgE and IgG reactivity to A, cow’s milk and egg allergens B, to nut‐, seed‐, fruit‐ and wheat allergens and C, fish‐ and shrimp allergens. Shown are IgE (ISU‐IgE) and IgG (ISU‐IgG) levels (color code) specific for the allergens determined in sera from the patients with hyper‐IgE syndromes (PGM3, STAT3) and control subjects
FIGURE 3
FIGURE 3
Induction of specific and dose‐dependent rat basophil leukemia (RBL) cell activation in PGM3 patients. Shown are mean percentages of total beta‐hexosaminidase (y‐axes) releases from RBL cells which had been loaded with serum IgE from PGM3 patients (patients 2, 5) after stimulation with different allergen concentrations (x‐axes). Furthermore, negative controls (cells plus allergen only; cells plus serum only; cells plus medium only) and positive controls (loading with serum from a patient with clinically relevant sensitization to the tested allergen, pos control) were performed (x‐axes)
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References

    1. Ozcan E, Notarangelo LD, Geha RS. Primary immune deficiencies with aberrant IgE production. J Allergy Clin Immunol. 2008;122:1054‐1062. - PubMed
    1. Valenta R, Karaulov A, Niederberger V, et al. Molecular aspects of allergens and allergy. Adv Immunol. 2018;138:195‐256. - PubMed
    1. Lyons JJ, Milner JD. Primary atopic disorders. J Exp Med. 2018;215(4):1009‐1022. - PMC - PubMed
    1. Castagnoli R, Lougaris V, Giardino G, et al. Inborn errors of immunity with atopic phenotypes: a practical guide for allergists. World Allergy Organ J. 2021;14(2):100513. doi: 10.1016/j.waojou.2021.100513 - DOI - PMC - PubMed
    1. Ponsford MJ, Klocperk A, Pulvirenti F, et al. Hyper‐IgE in the allergy clinic–when is it primary immunodeficiency? Allergy. 2018;73(11):2122‐2136. - PubMed

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