Abstract Details

Title Defining the CSF Cytokine and Chemokine Signature of Neurosarcoidosis

Topic Autoimmune Neurology

Presentation(s) S38 - Autoimmune Neurology: Peripheral Autoimmunity, Paraneoplastic Disease, Checkpoint Inhibitors, and Neurosarcoidosis (5:06 PM-5:18 PM)

Poster/Presentation
Number 009

Background

Studies investigating cytokines/chemokines in neurosarcoidosis patients’ CSF reported elevations of IL-2, IL-6, IL-8/CXCL8, IL-10, BAFF, CXCL10, IFN-gamma, and TNF-alpha. These studies have evaluated a restricted number of analytes in relatively small numbers of disease and control patient samples.

Objective

To describe the cytokine/chemokine profile in cerebrospinal fluid (CSF) of patients with neurosarcoidosis.

Design/Methods

We performed a systematic analytical validation of a multiplexed automated CSF cytokine/chemokine immunoassay system with 17 analytes (IL1b, IL2, IL4, IL5, IL6, IL8/CXCL8, IL10, IL12p70, IL13, IL17A, GM-CSF, TNF-alpha, IFN-gamma, CXCL9, CXCL10, CXCL13, BAFF) and comprehensive stability assessment. We tested CSF of patients with probable or definite CNS neurosarcoidosis evaluated at Mayo Clinic (01/2011-02/2023). Evidence of active disease (symptomatic patients with gadolinium enhancement or inflammatory CSF) and immunotherapies were documented. CSF from patients with non-inflammatory disorders were used as controls. Comparisons were made with the Wilcoxon rank-sum test.

Results

CSF cytokines/chemokines were stable at 4^oC for at least 30 days, except for IL1b, IL2, IL10, and CXCL10. Thirty-two neurosarcoidosis patients were studied (59.4% female; median age 59 years [range, 19-81]); control patients were 38.2% female (median age 74 years [21-87]). Gadolinium enhancement was present in 31 (96.9%) and CSF was inflammatory in 28 (87.5%). IL-6, BAFF, CXCL9, CXCL10, CXCL13, GM-CSF, IFN-gamma, and TNF-alpha levels were significantly elevated in CSF from neurosarcoidosis patients compared with controls (p<0.0001). In addition, IL-2 (p=0.0002), IL-8/CXCL8 (p=0.0008), IL-10 (p=0.0005) and IL-13 (p=0.0018) also exhibited significantly higher levels in the neurosarcoidosis group.

Conclusions

Neurosarcoidosis is associated with significant CSF elevation of cytokines and chemokines associated with Th1 response, B-cell, follicular T-cell, and macrophage activation. Although use of TNF-alpha inhibitors improved outcomes, some patients do not have a complete response or develop neutralizing antibodies. Cytokine/chemokine signatures may guide differential diagnosis and provide novel targets for treatment.

Authors/Disclosures
Georgios Mangioris, MD (Mayo Clinic) PRESENTER	Dr. Mangioris has nothing to disclose.
Sean J. Pittock, MD (Mayo Clinic Dept of Neurology)	Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech, Inc.. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage Therapeutics, Inc.. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prime Therapeutics. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche/Genentech. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MedImmune/Viela Bio. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys Therapeutics. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche/Genentech. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB, Inc. Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffman/LaRoche AG. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genetech. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for F. Hofman/LaRoche. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arialys. The institution of Dr. Pittock has received research support from Grifols. The institution of Dr. Pittock has received research support from NIH. The institution of Dr. Pittock has received research support from Viela Bio/MedImmune/Horizon. The institution of Dr. Pittock has received research support from Alexion Pharmaceuticals. The institution of Dr. Pittock has received research support from F. Hoffman/LaRoche/Genentech. The institution of Dr. Pittock has received research support from NovelMed. The institution of Dr. Pittock has received research support from AstaZeneca. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received publishing royalties from a publication relating to health care.
Binxia Yang (Mayo clinic)	No disclosure on file
Allen J. Aksamit, Jr., MD, FAAN (Mayo Clinic)	Dr. Aksamit has nothing to disclose.
Divyanshu Dubey, MD, FAAN (Mayo Clinic)	The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from UCB. Dr. Dubey has received research support from David J. Tomassoni ALS Research Grant Program . Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care.
Eoin P. Flanagan, MBBCh, FAAN (Mayo Clinic)	The institution of Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. The institution of Dr. Flanagan has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pharmacy times. The institution of Dr. Flanagan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for UCB. The institution of Dr. Flanagan has received research support from Viela Bio. The institution of Dr. Flanagan has received research support from UCB. The institution of Dr. Flanagan has received research support from Roche. Dr. Flanagan has received publishing royalties from a publication relating to health care. Dr. Flanagan has a non-compensated relationship as a Member of medical Advisory Board with The MOG Project that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Journal of The Neurologic Sciences that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Neuroimmunology Reports that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial Board Member with Neurology, Neuroimmunology Neuroinflammation (N2) Journal that is relevant to AAN interests or activities.
Alfonso S. Lopez, MD (Mayo Clinic)	Dr. Lopez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Lopez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech .
Andrew McKeon, MD (Mayo Clinic)	The institution of Dr. McKeon has received research support from National Institutes of Health. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received publishing royalties from a publication relating to health care.
John R. Mills, MD, PhD (Mayo Clinic)	The institution of Dr. Mills has received research support from Werfen Diagnostics. Dr. Mills has received intellectual property interests from a discovery or technology relating to health care.
Ivana Vodopivec, MD (F Hoffmann-La Roche AG)	Dr. Vodopivec has received personal compensation for serving as an employee of Roche. An immediate family member of Dr. Vodopivec has received personal compensation for serving as an employee of Novartis. Dr. Vodopivec has stock in Roche.
W. O. Tobin, PhD, MBBCh, BAO, FAAN (Mayo Clinic)	The institution of Dr. Tobin has received research support from Mallinckrodt. Dr. Tobin has received publishing royalties from a publication relating to health care. Dr. Tobin has received personal compensation in the range of $500-$4,999 for serving as a Speaker with NeurologyLive.
Michel Toledano, MD (Mayo Clinic)	Dr. Toledano has nothing to disclose.
Anastasia Zekeridou, MD, PhD, FAAN (Neuroimmunology Laboratory, Mayo Clinic)	The institution of Dr. Zekeridou has received research support from Roche/Genentech. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care.