Sarosh R. Irani FRCP, DPhil, FEAN

Sarosh Irani is a clinician scientist who leads the Oxford Autoimmune Neurology Group to better manage and study autoantibody-mediated diseases of the nervous system.

Dr. Irani undertook clinical training in Oxford and London, with a DPhil in Oxford and Fulbright postdoctoral position in UCSF. He has made several clinical discoveries including the recognition of faciobrachial dystonic seizures and other distinctive psychopathological features associated with NMDAR-antibody encephalitis. In the laboratory, he has led the discovery of LGI1- and CASPR2-antibodies, their associated HLA associations and the roles of B cells in the pathogenesis of autoimmune forms of encephalitis and neuromyelitis optica. He was 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. He runs the UK’s major clinic for antibody mediated CNS diseases and continues to explore the immunobiology and neuroscience which underlie the autoimmune neurological diseases.

Dr. Irani is a consultant neurologist and clinician-scientist with clinical and laboratory experiences in the field of autoantibody-mediated diseases of the nervous system, in particular the central nervous system. He runs a dedicated clinic for the care of these patients, with a neuropsychiatrist and an encephalitis nurse. In parallel, Dr. Irani runs a research group of clinicians and scientists to learn more about the origins and treatments of these diseases. More than 95% of his patients participate in research projects, from which they make direct and key contributions to the progress of the field.

Dr. Irani's work has:

1. Discovered new autoantibodies such as those which target LGI1 and CASPR2.¹
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,^2,3 and in the seizure semiologies in patients with LGI1-antibodies.^4–6 These observations improve recognition of patients with encephalitis.
3. In conjunction, he studies the cellular and humoral human immunology to understand the basis of these diseases.⁷ To date, he and his team have described some of medicine’s strongest genetic (HLA) associations in patients with these autoantibodies⁸ and the potential of patient B cells in circulation to produce the autoantibodies in these conditions.^9,10 In addition, they 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.¹¹ Dr. Irani anticipates ongoing work towards determining the mechanisms underlying aetiology and propagation of these conditions will allow the rational selection of future immunotherapies.

References

1. Irani, S. R. et al. Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan’s syndrome and acquired neuromyotonia. Brain 133, 2734–2748 (2010).
2. Varley, J. A. et al. The Movement disorder associated with NMDAR antibody-encephalitis is complex and characteristic: an expert video-rating study. Journal of Neurology, Neurosurgery & Psychiatry (2018) doi:10.1136/jnnp-2018-318584.
3. Al-Diwani, A. et al. The psychopathology of NMDAR-antibody encephalitis in adults: a systematic review and phenotypic analysis of individual patient data. The Lancet Psychiatry 6, 235–246 (2019).
4. Irani, S. R. et al. Faciobrachial dystonic seizures: the influence of immunotherapy on seizure control and prevention of cognitive impairment in a broadening phenotype. Brain 136, 3151–3162 (2013).
5. Irani, S. R. et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Annals of Neurology 69, 892–900 (2011).
6. Thompson, J. et al. The importance of early immunotherapy in patients with faciobrachial dystonic seizures. Brain 141, 348–356 (2018).
7. Sun, B., Ramberger, M., O’Connor, K. C., Bashford-Rogers, R. J. M. & Irani, S. R. The B cell immunobiology that underlies CNS autoantibody-mediated diseases. Nat Rev Neurol 16, 481–492 (2020).
8. Binks, S. et al. Distinct HLA associations of LGI1 and CASPR2-antibody diseases. Brain 67, 641–22 (2018).
9. Wilson, R. et al. Condition-dependent generation of aquaporin-4 antibodies from circulating B cells in neuromyelitis optica. Brain 141, 1063–1074 (2018).
10. Makuch, M. et al. N-methyl-D-aspartate receptor antibody production from germinal center reactions: Therapeutic implications. Annals of Neurology 83, 553–561 (2018).
11. Ramberger, M. et al. Distinctive binding properties of human monoclonal LGI1 autoantibodies determine pathogenic mechanisms. Brain 143, 1731–1745 (2020).