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Background: Anti-N-Methyl-d-aspartate receptor (NMDAR) autoimmune encephalitis (NMDAR AE) is an autoimmune disease characterized by severe psychiatric and neurological symptoms. While the pathogenic role of antibodies (Abs) directed against the GluN1 subunit of NMDAR is well described in this disease, the immune mechanisms involved in the generation of the autoimmune B cell response, especially the role of T helper cells, are poorly understood. Previously, we developed a B-cell-mediated mouse model of NMDAR AE by immunization with a GluN1359–378 peptide that drives a series of symptoms that recapitulate AE such as anxiety behaviour and spatial memory impairment. Results: In this mouse model, we identified anti-GluN1-specific CD4+ but also CD8+ T cells in both spleen and meninges. T helper cells have a polyfunctional profile, arguing for a T and B cell crosstalk to generate anti-GluN1 pathogenic Abs. Interestingly, proteomic analysis of AE meninges showed enrichment of differentially expressed proteins in biological processes associated with B cell activation and cytokine signalling pathways. Conclusions: This study identified, for the first time, a potential contribution of T helper cells in the pathology of NMDAR AE and paved the way for the development of future tolerogenic approaches to treat relapses. [ABSTRACT FROM AUTHOR]

Keywords: allergy; basophil activation test; diagnosis; standardisation EN allergy basophil activation test diagnosis standardisation 1055 1058 4 10/09/23 20231001 NES 231001 Key messages Adherence with guidelines was achieved for sample collection, transport and completion time. Priority needs for improvement are the standardisation of control validation and allergen concentrations tested. As mentioned by Eberlein et al.,[6] combinations of markers are needed for an accurate gating strategy; for example CCR3 SP + sp /CD3 SP neg sp , CRTH2 SP hi sp /CD3 SP neg sp , CD123 SP hi sp /HLA-DR SP neg sp or IgE SP + sp /CD203c SP + sp . ACKNOWLEDGEMENTS We thank the participants who completed the survey and the AllergoBioNet network for supporting the study: Dr Thierry Tabary, Dr Lorna Garnier, Dr Yannick Chantran, Dr Mylene De Saint Jore, Dr Claude Lambert, Dr Stéphanie Rogeau, Dr Moïse Michel, Dr Joana Vitte, Dr Martine Pernollet, Dr Jean Milhes, Dr Céline Beauvillain, Dr Béatrice Uring-Lambert, Dr Delphine Mariotte, Dr Mirjana Radosavljevic and Dr Pol André Apoil. [Extracted from the article]