September 2024 - Maria Regina Strobl

Dipl.-Ing. Maria Regina Strobl

MedUni Wien RESEARCHER OF THE MONTH September 2024

The induction of IgE-blocking allergen-specific IgG4 is considered a hallmark of clinically effective allergen-specific immunotherapy (AIT), which is the only curative treatment option for IgE-mediated allergy. In our recently published study “The role of IgG1 and IgG4 as dominant IgE-blocking antibodies shifts during allergen immunotherapy” we regularly monitored the allergen-specific IgG response during AIT and revealed that IgG1 antibodies dominated in terms of concentration and IgE-inhibitory capacity in the first 12 months of therapy. Allergen-specific IgG4 took over afterwards. Additionally, we were able to show that the avidity of allergen-specific IgG1 was already high at the beginning of AIT and did not substantially increase during the following 3 years of treatment. Moreover, we found that the binding strength of IgG1 is superior to that of IgG4. Our findings contribute to a deeper understanding of immunological processes that lead to allergen tolerance induced by AIT.

Selected Literature

1. Strobl MR, Demir H, Sanchez Acosta G, Drescher A, Kitzmüller C, Möbs C, et al. The role of IgG1 and IgG4 as dominant IgE-blocking antibodies shifts during allergen immunotherapy. J Allergy Clin Immunol. 2023;151(5):1371-8 e5.

2. Shamji MH, Valenta R, Jardetzky T, Verhasselt V, Durham SR, Wurtzen PA, et al. The role of allergen-specific IgE, IgG and IgA in allergic disease. Allergy. 2021;76(12):3627-41.

3. Durham SR, Shamji MH. Allergen immunotherapy: past, present and future. Nat Rev Immunol. 2023;23(5):317-28.

4. Nouri-Aria KT, Wachholz PA, Francis JN, Jacobson MR, Walker SM, Wilcock LK, et al. Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and blocking IgG activity. J Immunol. 2004;172(5):3252-9.

5. James LK, Till SJ. Potential Mechanisms for IgG4 Inhibition of Immediate Hypersensitivity Reactions. Curr Allergy Asthma Rep. 2016;16(3):23.

6. Shamji MH, Kappen J, Abubakar-Waziri H, Zhang J, Steveling E, Watchman S, et al. Nasal allergen-neutralizing IgG4 antibodies block IgE-mediated responses: Novel biomarker of subcutaneous grass pollen immunotherapy. J Allergy Clin Immunol. 2019;143(3):1067-76.

7. Sanchez Acosta G, Kinaciyan T, Kitzmuller C, Mobs C, Pfutzner W, Bohle B. IgE-blocking antibodies following SLIT with recombinant Mal d 1 accord with improved apple allergy. J Allergy Clin Immunol. 2020;146(4):894-900 e2.

8. Strobl MR, Demir H, Stadlmayr G, Stracke F, Hoelzl R, Bohle B, et al. Affinity matters for IgE-blocking activity of allergen-specific antibodies. Allergy. 2023;78(9):2543-6.

9. Strobl MR, Vollmann U, Eckl-Dorna J, Radakovics A, Ibl V, Schnurer M, et al. Identification of apple cultivars hypoallergenic for birch pollen-allergic individuals by a multidisciplinary in vitro and in vivo approach. Clin Transl Allergy. 2022;12(8):e12186.

10. Li X, Lee EJ, Lilja S, Loscalzo J, Schafer S, Smelik M, et al. A dynamic single cell-based framework for digital twins to prioritize disease genes and drug targets. Genome Med. 2022;14(1):48.

11. Zettl I, Ivanova T, Strobl MR, Weichwald C, Goryainova O, Khan E, et al. Isolation of nanobodies with potential to reduce patients' IgE binding to Bet v 1. Allergy. 2022;77(6):1751-60.

12. Husa AM, Strobl MR, Strajeriu A, Wieser M, Strehl S, Fortschegger K. Generation of CD34 Fluorescent Reporter Human Induced Pluripotent Stem Cells for Monitoring Hematopoietic Differentiation. Stem Cells Dev. 2018;27(19):1376-84.