MedH researcher awarded the Cozzarelli Prize 2024

Jakob Theorell at the Department of Medicine, Huddinge, is the first author of the prize-winning article. His group works with autoimmune encephalitis, both very patient-oriented and, as in this case, more concerning the underlying immunological mechanisms of the diseases. Autoimmune encephalitis is unusual in that the autoimmune reaction is directed against a single protein, which when knocked out in the brain often produces powerful, sudden symptoms, such as epilepsy or psychosis, which are not on a par with the often modest inflammation noted in test results.

"Our findings now emphasise this further, by showing that an extremely large proportion of all antibody-producing cells in the cerebrospinal fluid (which surrounds the brain) produce autoantibodies and that the main exhaustion of these cells occurs in the blood. This means that with clinically used testing methods, it may appear that there is no inflammation at all in the brain, when in fact there is a small group of cells pumping out huge amounts of antibodies with direct potential to cause disease," says Jakob, explaining how the research is now progressing:

"One consequence of our results is that I, together with neurological colleagues and the Department of Clinical Immunology at Karolinska University Hospital, have set up a method for counting antibody-producing cells in the cerebrospinal fluid. We are now evaluating this method, which has been in clinical use for six months. We are also working to understand more about the immune cell traffic to the brain in humans. We are doing this both to find new ways to prevent the pathogenic (disease-causing) cells from reaching the brain and to increase our diagnostic accuracy."

In the future, researchers hope to test the lymph nodes of the neck for autoantibodies, as lymph nodes seem to be directly involved in the inflammatory processes of autoimmune encephalitis.

Publication

Ultrahigh frequencies of peripherally matured LGI1- and CASPR2-reactive B cells characterize the cerebrospinal fluid in autoimmune encephalitis J. Theorell, R. Harrison, R. Williams, M.I.J. Raybould, M. Zhao, H. Fox, A. Fower, G. Miller, Z. Wu, E. Browne, V. Mgbachi, B. Sun, R. Mopuri, Y. Li, P. Waters, C.M. Deane, A. Handel, M. Makuch, & S.R. Irani. Proc. Natl. Acad. Sci. U.S.A. 121 (7) e2311049121, https://doi.org/10.1073/pnas.2311049121 (2024).