(Vienna, 10-05-2023) Common Variable Immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency in humans. Patients suffer from recurrent infections of the upper and lower respiratory tract but many of them also develop more severe symptoms such as granulomas, lymphomas and autoimmune diseases. An international team of researchers led by MedUni Vienna has now discovered why some CVID patients develop an autoimmune disease and others do not. The results of the study were published in the journal Cell Reports.
Common Variable Immunodeficiency (CVID) is characterized by a lack of antibodies (IgG, IgA and sometimes IgM). As well as being susceptible to infections, people with CVID are at higher risk of developing an autoimmune disease. B lymphocytes (B cells) are considered key players in this malfunction of the immune system, in which the body's own structures are attacked: autoreactive B cells need to be censored during B-cell development in order to prevent autoimmunity.
"Although autoimmune diseases 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 diseases," says principal investigator Ola Grimsholm from the Institute of Pathophysiology and Allergy Research at the Centre for Pathophysiology, Infectiology and Immunology at MedUni Vienna. It was shown that the central B-cell tolerance in the bone marrow is intact, but contrarily that peripheral B-cell selection in the germinal centre is defective. This was corroborated by the severely reduced number of somatic mutations in the B-cell receptor and especially true for replacement mutations in those patients with autoimmune diseases.
"Finally, our in vitro activation data could support mechanistically why the process of somatic hypermutation is not working optimally in these patients. In summary, our data can at least partially explain why certain patients with CVID are prone to develop autoimmune disease," says Ola Grimsholm, ahead of more in-depth studies on the topic.
Publication: Cell Reports
Defective peripheral B cell selection in common variable immune deficiency patients with autoimmune manifestations
Vanda Friman, Isabella Quinti, Alexey N. Davydov, Mikhail Shugay, Chiara Farroni, Erik Engström, Shirin Pour Akaber, Sabina Barresi, Ahmed Mohamed, Federica Pulvirenti, Cinzia Milito, Guido Granata, Ezio Giorda, Sara Ahlström, Johanna Karlsson, Emiliano Marasco, Valentina Marcellini, Chiara Bocci, Simona Cascioli, Marco Scarsella, Ganesh Phad, Andreas Tilevik, Marco Tartaglia, Mats Bemark, Dmitriy M. Chudakov, Rita Carsetti,
Ola Grimsholm
DOI: https://doi.org/10.1016/j.celrep.2023.112446