[WCN21;81;443]

The B Cell Biology Underlying Autoantibody-Mediated Diseases: Pathogenesis & Therapeutic Implications

Sarosh Irani

I am Head of the Oxford Autoimmune Neurology Group, and clinician-scientist with both clinical and laboratory interests in the autoantibody-mediated diseases of the nervous system, in particular the central nervous system. I run a dedicated clinic for the care of these patients and, in parallel, a research group of clinicians and scientists to study origins of these diseases and improve patient treatments.

Our work has:

1. Discovered new autoantibodies such as those which target LGI1 and CASPR2.
2. Shown that autoantibody specificities can have a remarkably close relationship with the patient phenotype. For example, the psychopathological features and movement disorder in patients with NMDAR-antibodies, and in the seizure semiologies in patients with LGI1-antibodies. These observations improve recognition of patients with encephalitis.
3. In conjunction, we study the cellular and humoral human immunology to understand the basis of these diseases.

To date, we have described some of medicine’s strongest genetic (HLA) associations in patients with these autoantibodies and the potential of patient B cells in circulation to produce the autoantibodies in these conditions. In addition, we have used the immune cells within patient ovarian tumours to better understand the aetiology of these diseases. We are using these foundations to understand the breaks in immune tolerance and developing methods to rapidly generate patient-derived monoclonal antibodies to precisely explore the neuroscience mechanisms by which the antibodies cause disease.

We anticipate ongoing work towards determining the mechanisms underlying aetiology and propagation of these conditions will allow the rational selection of future immunotherapies.