Clinical and immunological phenotyping, analysis of autoantigens and T and B cell communication

Project description

The CURE-ME research network will contribute to a better understanding of the pathomechanisms of post-infectious ME/CFS, to identify biomarkers for specific, early diagnosis and to identify targets for new treatment concepts. ME/CFS is a chronic, complex disease with a heterogeneous presentation that affects adults as well as children and adolescents. It is unclear whether the underlying mechanisms are similar in adolescents and adults. However, infections with the Epstein-Barr Virus (EBV) in all age groups are associated with the occurrence of ME/CFS and the formation of antibodies with homologies to autoantigens, i.e. autoantibodies (aabs). In addition to this direct promotion of aabs, an indirect effect of EBV through impaired expression of inhibitory checkpoint molecules (CM) of autoreactive B cells is conceivable in the context of SARSCoV-2 infections. These CMs, in turn, form a central component of T cell control. The aim of the CURE-ME research network is to investigate the connection between EBV, EBV-induced, cross-reactive and other autoantigens as causes of aberrant T and B cell reactions and autoimmunity in ME/CFS. To this end:

1) age-specific and common EBV-aab profiles are to be characterised;

2) the influence of impaired T-B cell communication and CM expression on the activation of autoreactive B cells is to be investigated; and

3) an increased frequency of EBV-cross-reactive and other autoreactive B cells is to be detected and specifically inhibited.

At the Charité - University Medicine Berlin, in addition to clinical and immunological phenotyping of neuronal autoantigens, it is being investigated whether impaired T-B cell communication occurs in ME/CFS and how this is associated with clinical features and aab profiles. Furthermore, a functional characterisation and manipulation of antigen-specific B cells is being carried out.

(Description adapted from project website: see link above)