好色先生

好色先生

Explore the latest content from across our publications
Join The AAN

Log In

Forgot Password?
Create New Account

Loading... please wait

Abstract Details

Extensive Characterization of HSV1 Antibody Responses in Herpes Encephalitis Reveals Compartmentalization in CSF and Predicts Development of Post-herpes Autoimmune Encephalitis
Autoimmune Neurology
S7 - Autoimmune Encephalitis (3:54 PM-4:06 PM)
003
Herpes-simplex-virus-1 (HSV1) can cause recurrent cold sore (periphHSV) or encephalitis (HSE). HSE can be complicated by autoimmune encephalitis (postHSE-AE). The mechanisms of HSE and postHSE-AE remain unclear. 
Characterize the HSV1-antibody responses in periphHSV, HSE and postHSE-AE.
We extensively profiled HSV1-antibody responses in serum and CSF of 45 HSE (12 who developed, 33 who did not develop postHSE-AE, at onset and 1month), and in serum of 12 periphHSV. We analyzed Ig classes/sublasses (IgA, IgG1-4, IgM), capacity to bind Fc receptors (FcgR2A/2B/3A/3B) and mediate Antibody-Dependent Cellular/Neurotrophil Phagocytosis (ADCP/ADNP), Complement Deposition (ADCD) and NK-cells activation (ADNKA). Antibody features were compared across groups and compartments (serum and CSF) and correlated with disease severity. Neuronal death of HSV1-infected cultured neurons treated with IgG from HSE, periphHSV or healthy controls (with/out innate cells) was quantified by confocal microscopy. 

Despite lower CSF responses at HSE onset, at 1 month CSF responses significantly increased (p<0.001), whereas serum responses remained stable. PLSDA/LASSO analyses identified ADCD in serum and ADCP in CSF as the most different features across compartments. Higher CSF-ADCP correlated with HSE severity (Spearman-coefficient=0.49, p=0.03). 

Compared to HSE, periphHSV showed higher serum ADNKA and FcgR3A-binding (p<0.01), despite similar IgG titers. Instead, serum ADCP was increased in HSE (p<0.05).  

Patients who developed PostHSE-AE showed higher serum/CSF titers, ADCD, ADNP and FcgR binding (p<0.01), compared to those who did not develop PostHSE-AE. 

HSV1-infected neurons treated with HSE-derived IgG (but not from periphHSV or healthy controls, p<0.01) caused increased neuronal death. Effects of innate effector cells will also be presented. 
During HSE, CSF-HSV1-responses are characterized by phagocytosis-activating antibodies, which correlates with HSE severity and predicts PostHSE-AE. Enrichment of NK-activating antibodies in periphHSV suggests a role for NK in protecting the brain from HSE. Antibodies from HSE cause increased neuronal death, likely contributing to antigen release and development of neuronal autoimmunity. 
Authors/Disclosures
Marianna Spatola, MD, PhD (FUNDACIÓ DE RECERCA BIOMEDICA CLÍNIC IDIBAPS)
PRESENTER 		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.
Laura Marmolejo Alcaide Miss Marmolejo Alcaide has nothing to disclose.
Chiara Milano, MD Dr. Milano has nothing to disclose.
Jesus Planaguma The institution of Dr. Planaguma has received research support from Spanish national Institute of Heath.
Esther Aguilar, Bachelor of science Mrs. Aguilar has nothing to disclose.
Raquel Bello-Morales, PhD Dr. Bello-Morales has nothing to disclose.
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.
Thais Armangue, MD (IDIBAPS-HClinic) Dr. Armangue has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. The institution of Dr. Armangue has received research support from ISCIII(Spanish institute of health) -PI21/00316, Marato TV3, La Caixa Research Foundadion, Pablove Foundation (689368), Torrons Vicens Foundation (PFNR0144), 2021 Invest AEP.