MS Immuno-T: Developing a T cell-based blood test for enhanced diagnosis of multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory autoimmune condition characterised by progressive neurological dysfunction, affecting ~110,000 in the UK and ~2.8 million people globally. Primarily, patients present initial symptoms in young adulthood, a highly productive stage of life that significantly impacts the individual, their families and society. Disease prevalence is increasing ~2.4% annually across both developed and developing countries, imposing significant socioeconomic burdens on societies and healthcare providers. In addition, MS is frequently mis-diagnosed, with a large multi-centre study highlighting that 17-19% of subjects diagnosed with MS do not have the disease (Kaisey et al. 2019). Indeed, the diagnostic pathway for MS is complex, relying on both patient medical history and multiple costly and invasive examinations performed over 6-12 months. Due to the revised 2017 McDonald diagnostic criteria, many more people undergo lumbar punctures as part of their MS diagnostic journey. This allows a cerebral-spinal fluid sample to be assessed for oligoclonal bands or neurofilaments, diagnostic tests that achieve sensitivity of 80-87% depending on population. However, patients often report they find the lumbar puncture painful; in addition, 7.9% of procedures result in unintended complications requiring hospitalisations or time off work to recover. Whilst early correct diagnosis significantly improves outcome, currently there is no blood test for diagnosing MS. Latest scientific advancements have identified particular T cell responses as the critical driver of MS pathogenesis. Of note, a recent publication identified a mechanistic link between the Epstein-Barr virus (EBV) and MS (Lanz et al. Nature (2022)). In particular, their work identified that adaptive immune responses (antibodies and T cells) specific for a particular EBV protein (EBNA1) has the potential to cross-react to GlialCAM, a cell adhesion molecule expressed in the healthy central nervous system (CNS) by astrocytes and oligodendrocytes, and highly expressed in chronic-active plaques in MS brain lesions. Importantly, IFN-g-producing GlialCAM-specific T cell responses were only identified in MS patients not healthy donors, highlighting the potential for a novel T cell-based diagnostic test. ImmunoServ were awarded the Welsh Government funding to build upon these prior academic findings and standardise the approach to measuring GlialCAM-specific T cell responses, utilising ImmunoServ's Immuno-T platform. In collaboration with neurologists at the Cardiff & Vale University Heath Board and the Welsh Neuroscience Research Tissue Bank, an initial feasibility study was performed amongst pwMS and healthy donor / neurological control patients, which generated highly promising data warranting further validation. This project will perform clinical validation of the MS Immuno-T test to assess diagnostic performance in comparison to current standard of care diagnostics. Key milestones include initiating recruitment of patients querying MS diagnosis at two UK-based neurology clinics (months 0-3), completion of recruitment (21-24 months) and establishing a pathway to clinical adoption in the UK through involvement with CEDAR and the NHS Health Innovation Network (months 24-36). The main output will be a clinically validated diagnostic blood test for MS, the first of its kind worldwide, with additional UK benefits through high-skilled job retention, IP creation and patient access to innovative diagnostics.