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Abstract Details

Innate Immune Responses and Antibody Dynamics in an Animal Model of Anti-NMDAR Encephalitis
Autoimmune Neurology
S16 - Autoimmune Neurology: Immune Profiling and Antibody Detection (1:36 PM-1:48 PM)
004

To characterize antibody class/subclass dynamics and innate immune responses in a mouse model of anti-NMDAR encephalitis that closely resembles the human disease (Maudes et al, Brain 2025).
Anti-NMDAR encephalitis is driven by pathogenic IgG1 autoantibodies that disrupt neuronal function and reproduce disease features in passive and active immunization models. While these models have elucidated adaptive immune mechanisms and uncovered microglial involvement, the temporal dynamics of antibody classes/subclasses and the role of innate immunity remain unexplored.
Female C57BL/6 mice were immunized with an NMDAR peptide or saline plus AddaVax and pertussis toxin. NMDAR-specific IgM, IgG, and IgG subclasses (1-4) were quantified in serial sera (days 7-14-28-36-42 post-immunization) by flow cytometry. At days 14 and 42, brain innate immune infiltrates (neutrophils, macrophages, NK cells), microglial activation, complement, and IgG deposition were analyzed by confocal imaging. Antibody-dependent effector functions (phagocytosis by monocytes, neutrophils or microglia, complement activation) and Fcγ receptors (FcγR 1–4) binding were assessed at day 42 using flow cytometry.
Immunized mice, but not controls, developed serum NMDAR-autoantibodies (IgM, IgG) by day 14. IgM peaked at day 14 and declined, whereas IgG remained elevated through day 42, predominantly IgG1 and IgG2b. At day 42, these antibodies enhanced monocyte- and microglia-mediated phagocytosis (and to a lesser extent also neutrophil) and complement activation. Confocal microscopy revealed increased brain infiltration of neutrophils, macrophages, and NK cells at both time points, with elevated hippocampal microglial activation and IgG deposition at day 42, but not day 14. FcγR-antibody binding and brain complement deposition will be reported. 

Innate immune cells infiltrate the brain early after immune activation, coinciding with the rise of NMDAR-IgG antibodies that strongly activate innate effector functions. These findings suggest that innate immunity plays an active role in disease pathogenesis in this model of anti-NMDAR encephalitis.
Authors/Disclosures
Laura Marmolejo Alcaide
PRESENTER 		Miss Marmolejo Alcaide has nothing to disclose.
Mariona P. Pérez Comerón, Undergraduate student Miss Pérez Comerón has nothing to disclose.
Afnaan AlSabbry, MSc Mrs. AlSabbry has nothing to disclose.
Claudia Papi, MD (FRCB-IDIBAPS) Dr. Papi has nothing to disclose.
Chiara Milano, MD Dr. Milano has nothing to disclose.
Ana Beatriz Serafim, MSc Miss Serafim has received research support from Fundação para as ciências e tecnologia.
Jesus Planaguma Dr. Planaguma has nothing to disclose.
Esther Aguilar, Bachelor of science Mrs. Aguilar has nothing to disclose.
Lidia Sabater, PhD The institution of Dr. Sabater has received research support from Instituto de Salud Carlos III.
Estibaliz Maudes, PhD The institution of Dr. Maudes has received research support from Basque Government PhD fellowship. The institution of Dr. Maudes has received research support from ECTRIMS.
Josep O. Dalmau, MD, PhD, FAAN Dr. Dalmau has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas Research Institute of America. Dr. Dalmau has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen Research & Development . Dr. Dalmau has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for 好色先生. An immediate family member of Dr. Dalmau has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Dalmau has received research support from Sage Therapeutics. The institution of Dr. Dalmau has received research support from Edmond J.Safra Foundation . The institution of Dr. Dalmau has received research support from La Caixa Foundation. The institution of Dr. Dalmau has received research support from Spanish Ministry of Health (ISCIII). The institution of Dr. Dalmau has received research support from Euroimmun, Inc. Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care.
Marianna Spatola, MD, PhD, FAAN (FUNDACIÓ DE RECERCA BIOMEDICA CLÍNIC IDIBAPS) The institution of Dr. Spatola has received research support from Spanish National Health Institute (Carlos III), FIS grant. The institution of Dr. Spatola has received research support from Spanish National Institute of Health - Miguel Servet Grant. The institution of Dr. Spatola has received research support from La Caixa Foundation. The institution of Dr. Spatola has received research support from European Research Coucil.