Association of myeloid cell and gut-derived B-cell diversity with disease activity and severity in mulitple sclerosis

PD Dr. Chotima Böttcher

• B05

PD Dr. Carolin Otto

• B05

Project Summary

Multiple sclerosis (MS) exhibits a heterogeneity of clinical features, genetic and environmental risk factors, and mechanisms of tissue damage. One of the fundamental pathomechanisms involves cell and humoral mediated immune dysregulation. During the first and the second funding periods, we showed compartment-related phenotypic differences of MS myeloid cells as well as B cells as compared to other neurological diseases.
In the third funding period, we aim to investigate the association of diverse myeloid and B cells as well as molecular profiles with disease activity and severity in MS. Furthermore, we aim at exploring the cross talk between defined molecular markers, B and myeloid cells and their implications for compartmentalization of inflammati on in the CNS. To do so, firstly, we will use our streamlined mass cytometry workflow to perform indepth characterization of multiple immune cell types in CSF, peripheral blood and gut biopsies of a large observational cohort of patients with different neuroinflammatory conditions including MS. In addition, metabolomics and targeted proteomics will be also performed (Aim 1). Secondly, a multi-modal data analysis approach will be used to evaluate the correlation between defined cell phenotypes, metabolomics, proteomics and meta- and clinical data (Aim 2). Thirdly, to validate the findings in Aim 1 and 2, we will apply the analytical strategy developed in Aim 1 and 2 on two longitudinal studies of MS patients with 1) an ocrelizumab (OCRE) treatment and 2) a nutritional intervention study (Aim 3). Finally, cross talk between defined B and myeloid cells association with CNS compartmentalized inflammation will be evaluated in vitro (Aim 4). In sum, multi-modal datasets on single-cell and molecular profiles of treated or untreated MS patients, in comparison to other diseases, will improve the knowledge on MS neuroinflammation and its changes under different disease phases and modified conditions such as cell depletion therapy and nutritional intervention.