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Jakob Theorell, Ruby Harrison et al.
The research, ‘Ultrahigh frequencies of peripherally matured LGI1 & CASPR2-reactive B cells characterise encephalitis patient cerebrospinal fluid’, published in Proceedings of the National Academy of Sciences PNAS, sheds new light on the molecular mechanisms behind autoimmune encephalitis (AE) – a rare but serious neurological condition.
Led by Professor Sarosh Irani, the study brought together researchers across disciplines to investigate the properties of antibodies that cause AE. The team analysed over 150 antibodies isolated from the cerebrospinal fluid (CSF) of affected patients and discovered that, remarkably, around 80% were reactive to just two self-proteins: LGI1 and CASPR2. Professor Irani said:
I am very excited to see that my team won this prize for our publication, as it captures the essence of our patient-to-bench translational research programme.
Through our research, we found cells – which likely directly contribute to the patient’s autoimmune disease – at ultrahigh frequencies in the CSF. These form a potential target for improved therapeutics going forward.’
Other NDCN co-authors included: Jakob Theorell, Ruby Harrison, Robyn Williams, Meng Zhao, Hannah Fox, Andrew Fower, Georgina Miller, Zoe Wu, Eleanor Browne, Bo Sun, Patrick Waters, Adam Handel and Mateusz Makuch.
Researchers from the Oxford Protein Informatics Group (Department of Statistics), Dr Matthew Raybould and Professor Charlotte Deane, supported the bioinformatics analysis that characterised the antibodies’ genetic diversity and developmental origins. Their work helped reveal that the B cells likely began gaining self-reactivity while circulating in the bloodstream, before migrating to the central nervous system where they transformed into long-lived antibody-producing cells.
The Cozzarelli Prize in Biomedical Science is awarded annually to a PNAS publication judged by the academy’s Editorial Board to 'reflect scientific excellence and originality.