Institute of Virology

Clinical Virology, Valeria Falcone & Team

Circulating multimeric immune complexes during acute SARS-CoV-2 and chronic HBV infection

In the healthy individual immune complexes (IC) emerge in response to acute events such as viral infections leading to antigen expression and antibody production. Antibody mediated cellular immune functions are executed through FcγReceptors which fulfil important tasks such as phagocytosis, antibody dependent cytotoxicity (ADCC), and feeding of opsonized antigens into antigen presentation pathways. Following virus clearance, ICs are no longer generated and existing ICs vanish rapidly.

Persistent IC formation is a hallmark of various autoimmune diseases like systemic lupus erythematodes (SLE) but can also occur in chronic infectious diseases. Excess of ICs may result in unregulated prolonged FcγR signalling, excessive inflammation and finally tissue destruction. Recently, a robust and scalable FcγR test platform allowing for the detection and quantification of soluble circulating IC bioactivity has been developed in our lab (1). The assay has predictive capabilities regarding the severity of disease as shown for SLE but also severe COVID-19 (2, 3) indicating that ICs could represent a new biomarker for  certain diseases.

Presently, we are interested in understanding which role circulating ICs might play in chronic HBV infection, which is characterized by a co-production of high amounts of viral antigen and IgG antibodies. Hepatitis B virus (HBV) represents a leading cause of liver disease and continues to be a global public health threat. Several aspects of the innate as well as adaptive immune response to HBV and its trend-setting contribution to cure versus pathogenesis are still unclear. Triggering of specific Fcγ receptors (FcγRs) by circulating soluble ICs might contribute to immunopathogenesis but also to resolution of HBV replication and eventually convalescence. Together with the assessment of further laboratory and clinical parameters, soluble ICs detection could serve as a novel biomarker to predict the individual course of HBV chronic disease. Moreover, we intend to characterize the composition of bioreactive ICs, circulating in the serum of chronically infected patients at different stages of HBV disease, in terms of antigen, IgG subclass and IgG glycosylation state. 

Publications:

1. Chen H, Maul-Pavicic A, Holzer M, Huber M, Salzer U, Chevalier N, Voll RE, et al. Detection and functional resolution of soluble immune complexes by an FcgammaR reporter cell panel. EMBO Mol Med 2022;14:e14182.
2. Ankerhold J, Giese S, Kolb P, Maul-Pavicic A, Voll RE, Goppert N, Ciminski K, et al. Circulating multimeric immune complexes contribute to immunopathology in COVID-19. Nat Commun 2022;13:5654.
3. Kolb P, Giese S, Voll RE, Hengel H, Falcone V. Immune complexes as culprits of immunopathology in severe COVID-19. Med Microbiol Immunol 2023;212:185-191.

Team