Common variable immunodeficiency is the most common symptomatic primary immunodeficiency that is characterized by low levels of serum IgG, IgA and sometimes IgM. The patients suffer from recurrent infections of the upper and lower respiratory tract but many also develop more severe symptoms such as autoimmune manifestations, granulomas and lymphomas. Although autoimmune manifestations are commonly seen we still know little about B-cell selection in these patients. Therefore, we decided to investigate both central and peripheral B cell selection mechanisms in CVID by comparing patients with infection only to those with autoimmune manifestations. We demonstrate that the central B-cell tolerance is intact as measured by receptor editing. On the other hand, we found that peripheral B-cell selection in the germinal centre is defective. This was corroborated by the severely reduced number of somatic mutations, especially replacement mutations, in those patients with autoimmune manifestations. Finally, we show that in vitro activation of naive B cells in CVID B cells lead to suboptimal activation of the mismatch repair machinery, which could at least partially explain why the process of somatic hypermutation is not working optimally in these.
The fact that allergic inflammation and rhinovirus infection act synergistically in triggering airway inflammation gathered authors´ interest to develop a treatment that is effective for allergic as well as rhinovirus-induced rhinitis and asthma. Within their joint project they elaborate an innovative and efficient approach to catch pollen allergens at the nasal mucosa and hence stop allergen penetration into the body. Their concept was based on bispecific antibody conjugates capable to simultaneously bind to pollen allergens present in the air and to the transmembrane glycoprotein intercellular adhesion molecule 1 (ICAM-1), highly expressed on the respiratory epithelium of allergic patients. Since ICAM-1 is a major receptor for rhinovirus, bispecific antibody conjugates additionally protect against rhinovirus infection due to their receptor blocking capacity. Next, in vivo testing is envisaged to confirm the clinical efficacy of bispecific antibody conjugates for protection against allergic and viral airway diseases.
This research was funded by grants F4607, I3946-B33, F4613 and P29398 of the Austrian Science Fund (FWF) and by the Country of Lower Austria’s funded Danube Allergy research cluster (P09 and P13).
Ines Zettl, Tatiana Ivanova, Mohammed Zghaebi, Marina V. Rutovskaya, Isabella Ellinger, Oksana Goryainova, Jessica Kollárová, Sergio Villazala-Merino, Christian Lupinek, Christina Weichwald, Anja Drescher, Julia Eckl-Dorna, Sergei V. Tillib, Sabine Flicker.
Maria Butylina, PhD-student in the group of Prof. Dr. Peter Pietschmann, published recently her research on Nothobranchius furzeri, the turquoise killifish, in Gerontology.
Ines Zettl, Tatiana Ivanova, Maria R. Strobl, Christina Weichwald, Oksana Goryainova, Evgenia Khan, Marina V. Rutovskaya, Margarete Focke- Tejkl, Anja Drescher, Barbara Bohle, Sabine Flicker, Sergei V. Tillib
Allergy 2022 Jun;77(6):1751-1760. doi: 10.1111/all.15191. Epub 2021 Dec 16