Abstract Details

Title T cells and Acute Neuronal Damage Play a Relevant Role in the Immunopathology of Anti-GABA-B Receptor Encephalitis, Shaping Long-term Outcome

Topic Autoimmune Neurology

Presentation(s) S16 - Autoimmune Neurology: Immune Profiling and Antibody Detection (1:24 PM-1:36 PM)

Poster/Presentation
Number 003

Objective

To characterize the outcome and clinicopathological correlation of anti-GABA-B receptor encephalitis (anti-GABA-BR-E).

Background Anti-GABA-BR-E is characterized by neuropsychiatric symptoms, seizures and rapidly progressive dementia. In anti-NMDA receptor encephalitis, B cells and antibody-mediated mechanisms play a critical role, largely explaining the effectiveness of immunotherapy. However, in anti-GABA-BR-E, a limited treatment response has been recognized, suggesting additional pathogenic mechanisms.

Design/Methods Anti-GABA-BR-E patients were retrospectively and prospectively included from January 2011 to September 2024 at the Erasmus University Medical Center (The Netherlands). Demographics, tumor status, immunotherapy, and 1-year outcome (modified ranking scale [mRS]) were collected. Post mortem brain tissue, obtained at autopsy, of anti-GABA-BR-E cases and age- and sex-matched controls were analyzed by immunohistochemistry, quantifying B and plasma cells, T cells, IgG and neuronal damage.

Results Sixty-five patients were enrolled (36/65 female;55%, median age 68 years), of whom 45 (69%) had an underlying tumor and 48/65 (74%) received immunotherapy. Twenty-six of 36 treated patients (72%) with sufficient follow-up had an unfavorable (mRS≥3) 1-year outcome, including 5/6 (83%) non-paraneoplastic cases. Autopsy was performed in four patients, of whom three were untreated and one had a tumor. Immunopathology was characterized by perivascular lymphocytic cuffing, predominantly in the hippocampus and amygdala. A prominent CD8+ T cell response was observed infiltrating the brain parenchyma and perivascular area, with significantly higher positive cells/mm² in anti-GABA-BR-E compared to controls in the hippocampus (16.1 vs. 7.5, p=0.048) and amygdala (17.4 vs. 6.2, p=0.046). Deposition of granzyme B and amyloid precursor protein was observed in corresponding regions, compatible with acute T cell mediated neuronal and axonal damage. IgG producing B cells and plasma cells, were primarily located in perivascular regions.

Conclusions A limited treatment response is observed in the majority of anti-GABA-BR-E patients, probably explained by a strong cytotoxic T cell response with acute neuronal damage, in addition to the anticipated B cell–mediated antibody effects.

Authors/Disclosures
Robin W. van Steenhoven, MD PRESENTER	Dr. van Steenhoven has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. The institution of Dr. van Steenhoven has received research support from Autoimmune Encephalitis Alliance . The institution of Dr. van Steenhoven has received research support from Dutch Alzheimer's foundation. The institution of Dr. van Steenhoven has received research support from ItsME Foundation. The institution of Dr. van Steenhoven has received research support from Erasmus University Medical Center.
Jeroen Kerstens, MD	Mr. Kerstens has received research support from European Joint Programme on Rare Diseases. The institution of Mr. Kerstens has received research support from Erasmus Trust Fund.
Nina Fransen, MD, PhD	The institution of Dr. Fransen has received research support from Roche.
Valerie A. Quinot	No disclosure on file
Verena Endmayr, PhD	Dr. Endmayr has nothing to disclose.
Romana Hoeftberger (Medical University of Vienna)	Romana Hoeftberger has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology: Neuroimmunology and Neuroinflammation. Romana Hoeftberger has received personal compensation in the range of $500-$4,999 for serving as a speaker with BMS and UCB Biopharma.
Annemieke Rozemuller, MD, PhD	No disclosure on file
Maarten J. Titulaer, MD, PhD (Erasmus Medical Center)	The institution of Dr. Titulaer has received research support from Dutch Epilepsy Foundations (NEF 19-08). The institution of Dr. Titulaer has received research support from CSL Behring. The institution of Dr. Titulaer has received research support from UCB. The institution of Dr. Titulaer has received research support from Netherlands Organisation for Scientific Research (ZonMW, Memorabel initiative and E-RARE UltraAIE) . The institution of Dr. Titulaer has received research support from Horizon Therapeutics / Amgen. The institution of Dr. Titulaer has received research support from Dioraphte (charity). The institution of Dr. Titulaer has received research support from Guidepoint Global LLC. The institution of Dr. Titulaer has received research support from ArgenX. Dr. Titulaer has received intellectual property interests from a discovery or technology relating to health care. Dr. Titulaer has received publishing royalties from a publication relating to health care.

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