Departments of Neurology and Neurosciences, Mayo Clinic, Florida

Sarosh Irani is an Associate Professor, Honorary Consultant Neurologist and Wellcome Trust Intermediate Fellow with clinical and laboratory interests in the field of autoantibody-mediated diseases of the central nervous system. He sees patients with these disorders in a UK referral clinic and runs the Oxford Autoimmune Neurology Group (OANG) to learn more about the origins and treatments of these diseases.

His research has particularly focused on the phenotypes and immunology around autoantibodies found in forms of encephalitis which target LGI1, CASPR2, the NMDA-receptor and the GABAA-receptor, and, in patients with Neuromyelitis optica and antibodies against aquaporin-4. In particular, along a close collaborator in Oxford, Dr Patrick Waters, he developed a range of live cell based assays to characterise the autoantibodies, and optimise their detection. In addition, he described ‘Faciobrachial dystonic seizures’ as pathognomonic for the underlying LGI1-antibodies. These seizures show a superior response to immunotherapies versus antiepileptic drugs. Furthermore, their prompt cessation appears to alter the natural history of the condition, and prevent onset of cognitive impairment.

In these forms of encephalitis, recent clinical and imaging studies from the OANG and colleagues have revealed marked residual deficits in the recovery phase of disease. Therefore, to improve treatments, his group sought to better understand the immunology of these conditions. Using patient lymphocytes, the OANG developed in vitro assays to understand the relative contributions of circulating B cells and plasma cells to the production of the pathogenic antibodies, and clinical implications of these observations. In addition, OANG have produced clinical and immunogenetic studies to appreciate the involvement of T cells in these conditions. These models provide a platform to predict and assess the efficacy of therapeutic interventions, improve patient outcomes and understand the underlying immunobiology and aetiology.