PhD defence M. (Malou) Janssen

Multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) and  myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOGAD)  are demyelinating diseases of the central nervous system (CNS). In all three diseases an aberrant response of lymphocytes is thought to be the driving disease pathology.
Focusing on antigen specificity we showed, using CSF derived T cell lines, no significant antigen specific response was present towards previous suggested candidate antigens for either CD4+ or CD8+ T cell line. Looking at local recruitment we discovered Th17.1, sharing features of traditional Th1 and Th17, T cells are predominant in MS CNS, whereas they are low in peripheral blood of patients with clinically isolated syndrome  (CIS) and early MS. Treatment with a VLA-4 antibody resulted in selective upregulation of this subset, probably by hampering migration. Similar observations were done in CXCR3+ B cells: these cells were selectively upregulated in MS CSF, meninges and brain. CNS migration of these cells could be blocked by natalizumab as well. In pregnant MS patients, and not HC, memory B cells differentiated postpartum more frequently into professional antibody secreting cells (ASC).  These effects of pregnancy on B cells are likely to contribute to the increased relapse risk postpartum. 
In AQP4 positive NMOSD high levels of transitional B cells were found in samples close to relapse and this subset disappeared in patients treated with steroids. In patients with active disease, naive cells were more likely to differentiate into antibody secreting cells after TLR9 triggering.

Due to corona, the PhD defences do not take place publicly in the usual way in the Senate Hall or in the Professor Andries Querido Room. The candidates will defend their dissertation either in a small group or online.