F., Akman\Demir, G., Wick, M., & Wildemann, B. and the MS controls analyzed (36%, 95% CI 25%C48%). Conclusion The ABO blood group O antigen associates with higher anti\JCPyV antibody levels and may impact the risk of the later development of PML. The overrepresentation of blood group O in cases with PML was in line with a previous publication. Larger studies are warranted to assess a potential value of host genetic markers, such as the ABO status, for PML risk prediction during immunotherapy. Keywords: ABO blood group, natalizumab, PML, polyomavirus, progressive multifocal leukoencephalopathy Patients with multiple sclerosis and high anti\JC polyomavirus (JCPyV) antibodies in blood have an increased risk for the development of progressive multifocal leukoencephalopathy (PML) when treated for MS. We tested the hypothesis that type O blood group associates with anti\JCPyV antibody levels and the risk of developing PML in a monocentric cohort study. Anti\JCPyV antibody levels were found to be higher in individuals with blood group 0 compared with all other blood groups, and we noted a pattern for a higher frequency of blood group 0 in patients with PML. 1.?INTRODUCTION Progressive multifocal leukoencephalopathy (PML) is an opportunistic contamination of the brain caused by JC polyomavirus (JCPyV). PML occurs in patients with impaired cellular immune function such as patients with haematological Cyclosporin D disorders, patients infected with human immunodeficiency computer virus (HIV), and it is also a major concern in patients with multiple sclerosis (MS) treated with novel selective immunosuppressive therapies. In particular, the alpha4\integrin\blocking medication natalizumab associates with an increased risk of the development of PML (Major et?al., 2018), but cases of PML have also been observed with option medications such as fingolimod or dimethyl fumarate for the treatment of MS (Warnke et?al., 2015), or efalizumab for psoriasis (Schwab et?al., 2012), an observation that also hinders the development of several biologicals for immune mediated conditions. Detection of anti\JCPyV antibodies and the level of Cyclosporin D the anti\JCPyV antibody response FGF9 (so\called serum index values) (Plavina et?al., 2014; Warnke, Ramanujam, et?al., 2013) are accepted risk factors for the later development of PML. The reasons why higher antibody levels to JCPyV associate with higher risk of developing PML are not well understood. Host genetic factors may influence the anti\JCPyV antibody levels, and thus may be the underlying cause for such link. This has been shown for several human leukocyte antigen (HLA) class II variants presenting antigens to CD4+ T cells important in the defense against infections, but studies thus far were also underpowered to display associations outside the HLA region (Sundqvist et?al., 2014). PML is characterized by a lytic infection of oligodendrocytes and astrocytes and is often localized in the subcortical area between the gray and white matter. In this area, there are hemodynamic factors such as the reduction of vessel calibre that might be contributing factors facilitating the evasion of JCPyV. Cyclosporin D Early studies to detect anti\JCPyV antibodies were Cyclosporin D based on the fact that JCPyV can aggregate type O erythrocytes (hemagglutination inhibition assay). Since JCPyV can be present on the surface of B\lymphocytes, this may induce a clotting of lymphocytes and type O erythrocytes, which could associate with a higher likelihood of viral transmission to the brain in the small arteries in the subcortical area between the gray and the white matter in patients with type O erythrocytes. As such it has been hypothesized that patients with type O erythrocytes may be at higher risk of the later development of PML (Khoury et?al., 2013). In this monocentric cohort study, we assessed if type O blood Cyclosporin D group was associated with higher levels of anti\JCPyV antibodies. 2.?METHODS Stored sera available from routine clinical diagnostics at the Institute for Virology, University of Duesseldorf, collected between January.