Sarosh Irani

Research Summary

I am a Clinician-Scientist and Consultant Neurologist aiming to improve treatments and outcomes for patients with autoantibody-mediated diseases of the nervous system, and understand the biology behind these conditions. 

My research brings together patient-focused and more basic observations to understand multiple aspects of these diseases. Together with others I have studied autoantibodies which target LGI1, CASPR2, aquaporin-4, and the NMDA-, GABA_A- and glycine-receptors. More specifically, we have:

1. Discovered new autoantibodies such as those which target LGI1 and CASPR2 and hence defined immunotherapy-responsive conditions.
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 the seizure semiologies in patients with LGI1-antibodies notably Faciobrachial dystonic seizures. 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.
4. Used 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.

I have been awarded the Graham-Bull Prize in Clinical Science / Goulstonian Lectureship, from the Royal College of Physicians, and awards including the NIHR BRC Senior Clinical Fellowship and both Wellcome Intermediate and MRC Senior Clinical Fellowships. Our work has also been funded by the British Medical Association, Association of British Neurologists, multiple industry partners and by the very kind and generous donations from many of our patients.