Analysis of T-cell and B-cell receptor repertoires via single-cell RNA sequencing in patients with ME/CFS and post-COVID syndrome

Current evidence suggests that autoimmunity plays an important role in ME/CFS and post-COVID-Syndrome (PCS) and the similarity of symptoms suggests that both share a common pathophysiology. Detection of functional GPCR autoantibodies correlated with fatigue in PCS patients but so far, it is unclear why only subgroups of patients responded to autoantibody targeting treatments. Therefore, additional biomarkers are needed to delineate the role of autoimmunity in ME/CFS and PCS and to monitor the effectiveness of immunomodulatory treatments. One promising strategy in this context is the analysis of B-cell receptor (BCR) and T-cell receptor (TCR) repertoire of ME/CFS and PCS patients to detect potentially expanded or autoreactive clones that can be targeted. In contrast to bulk sequencing, single-cell RNA sequencing (scRNA-seq) is much more sensitive for the detection of clonally expanded immune cell receptors (IRs) as it allows the delineation of the complete BCR and TCRs in single cells and can provide information regarding the differentiation state and the metabolic activity of cells with distinct BCRs and TCRs. The investigators hypothesise that scRNA-Seq of the immune receptor repertoire could be a sensitive biomarker to assess the pathogenesis of ME/CFS and PCS and to monitor the response to immunomodulatory treatments. Within this project, they seek to identify clonally expanded and potentially autoreactive BCRs and TCRs in the peripheral blood from ME/CFS and PCS patients and map these to epitopes. BCR epitope pairs will furthermore be validated in-vitro and clonally expanded immune receptors will be compared between ME/CFS and PCS patients and healthy controls. Additionally, they plan to analyse the effect of treatments such as BC007 and corticosteroids on the TCR and BCR repertoire of ME/CFS and PCS patients regarding the potential elimination or functional attenuation of expanded and potentially autoreactive immune receptors.