Autoimmune encephalitis are a series of inflammatory diseases in the central nervous system in which the immune system mistakenly attack the proteins of the body, in this case, receptors of neurotransmitters or proteins of the neuronal surface. The action of the antibodies prevents the proper functioning of such proteins, which can cause the emergence of neuropsychiatric symptoms such as changes in behaviour, psychoses, convulsions and cognitive and memory deficit. The autoimmune diseases are the third part of all encephalitis cases worldwide and affect people at any age, although some subtypes appear mostly in children and young adults.
A study led by Lidia Sabater and the UB adjunct lecturer Josep Dalmau, both members of the Research Group on Pathogenesis of Autoimmune Neuronal Disorders at Clínic-IDIBAPS, has described a new type of autoimmune encephalitis unknown to date: encephalitis anti-GluK2. The first signatories of the paper, published in the journal Annals of Neurology, are Jon Landa and Mar Guasp, members of the mentioned group.
To date, sixteen autoimmune encephalitis affecting the central nervous system have been described. Ten of these were found in studies led by Josep Dalmau, and four out of these ten were found during the period the expert started in 2011 in Clínic-IDIBAPS and the UB. The new findings add a new autoimmune encephalitis on this list.
"We had a group of patients without a clear diagnostic but with symptoms in common. Their cerebellum was affected, a part of the brain that controls balance and movement. The patients presented vomit, headache and instability when walking", notes Josep Dalmau, also ICREA researcher and member of the Institute of Neurosciences of the UB. "What we found is that these patients produce antibodies against a sub-unit of the kainate receptor, GluK2, an that these antibodies alter the levels and the function of receptors, and therefore, these can be the ones to cause the clinical symptomatology".
A second part of the study, in collaboration with the Research Group on Neurophysiology led by the Xavier Gasull, professor at the Department of Biomedicine, showed that antibodies alter the electrical impulses that ease communication between neurons.
"Kainate receptors, together with the AMPA and NMDA receptors, belong to the family of glutamatergic ionotropic receptors", notes Lidia Sabater. The team led by Josep Dalmau had identified the antibodies that attack the NMDA receptor in 2007 and the AMPA receptor in 2009. "Since the AMPA, NMDA and kainate receptors are similar, we were not surprised to see there are antibodies against the latter", concludes Sabater.
To date, patients with encephalitis anti-GluK2 were thought to have idiopathic or potentially viral encephalitis, and did not receive the proper immunotherapy. This study facilitates the recognition of the syndrome and the use of the immunological treatment.
Jon Landa, Mar Guasp, Federico Míguez-Cabello, Joana Guimarães, Takayasu Mishima, Fumiko Oda, Frauke Zipp, Vladimir Krajinovic, Peter Fuhr, Jerome Honnorat, Maarten Titulaer, Mateus Simabukuro, Jesús Planagumà, Eugenia Martínez-Hernández, Thais Armangué, Albert Saiz, Xavier Gasull, David Soto, Francesc Graus, Lídia Sabater, Josep Dalmau. "Encephalitis with autoantibodies against the glutamate kainate receptors GluK2" . Annals of Neurology, May, 2021. Doi: 10.1002/ana.26098