Abstract Details

Title Sex-specific Differences in “Forever Chemical” Levels in Multiple Sclerosis, NMOSD, and MOGAD

Topic Autoimmune Neurology

Presentation(s) P2 - Poster Session 02 (3:00 PM-4:00 PM)

Poster/Presentation
Number 1-036

Objective

To investigate per- and polyfluoroalkyl substance (PFAS) concentrations in MS, AQP4-NMOSD, and MOGAD.

Background

PFAS are persistent immunotoxic/neurotoxic chemicals widely detectable in the US population and elevated in MS in Sweden.

Design/Methods

Serum PFHxS, PFOA, and PFOS were quantified in ACP (73 untreated RRMS, 35 NMOSD, 106 HC) and CMSAN (103 RRMS, 22 SPMS, 28 PPMS, 24 NMOSD, 48 MOGAD). Linear regression tested MS vs HC in ACP, MS vs NMOSD in both cohorts, and MS vs MOGAD in CMSAN, adjusting for age, sex, BMI, and smoking for normalized PFAS (mean=0, SD=1), including sex-stratified models. In 56 ACP RRMS females, associations between PFAS and sex-steroid metabolites were evaluated, and PFAS-correlated gene-expression signatures were examined.

Results

PFHxS was elevated in MS versus HC (ACP β=0.38, p=0.0025), NMOSD (ACP+CMSAN β=0.52, p=6.3×10?5), and showed a trend versus MOGAD (CMSAN β=0.31, p=0.058).

In females, PFHxS was higher versus HC (β=0.44, p=0.0058) and NMOSD (ACP+CMSAN β=0.53, p=0.00047), but not MOGAD (β=0.42, p=0.061); No significant differences were observed among males.

PFOA was not significantly elevated versus HC (ACP β=0.16, p=0.054), but was higher versus NMOSD (ACP+CMSAN β=0.76, p=6.8×10??) and MOGAD (β=0.33, p=0.010).

Among females, PFOA showed a trend versus HC (β=0.24, p=0.075) and was higher versus NMOSD (ACP+CMSAN β=0.80, p=2.9×10?7) and MOGAD (β=0.60, p=0.013); males showed no differences.

PFOS did not differ versus HC (β=0.14, p=0.32) and was higher versus NMOSD (ACP+CMSAN β=0.64, p=3.3×10?7) but not MOGAD (β=0.08, p=0.60), with less consistent sex-specific patterns.

Exploratory analyses identified MS×PFOA interactions for several sex-steroid metabolites, and tentative enrichment of neuronal membrane pathways among PFAS-correlated genes.

Conclusions

PFHxS and PFOA were elevated in MS versus HC, NMOSD, and MOGAD, specifically among females.

Exploratory findings suggest plausible pathways linking PFAS exposure to MS. Multi-ethnic and longitudinal studies are needed to expand generalizability and clarify temporality and causality.

Authors/Disclosures
Federico Montini, MD, PhD (Mayo Clinic College of Medicine and Science) PRESENTER	Dr. Montini has nothing to disclose.
Charles F. Spurlock III, PhD (Decode Health)	Dr. Spurlock has received personal compensation for serving as an employee of Decode Health. Dr. Spurlock has received personal compensation for serving as an employee of New York University. Dr. Spurlock has received personal compensation for serving as an employee of IQuity Labs. Dr. Spurlock has stock in Decode Health. Dr. Spurlock has stock in IQuity Labs. The institution of Dr. Spurlock has received research support from National Institutes of Health.
Christine B. Ryan, PhD, Medical student	Dr. Ryan has nothing to disclose.
Jessica Cooke Bailey	Jessica Cooke Bailey has nothing to disclose.
Erika F. Trapl, PhD	An immediate family member of Dr. Trapl has received personal compensation for serving as an employee of Philips International. The institution of Dr. Trapl has received research support from NIH.
Guzel Shaginurova, PhD	Dr. Shaginurova has nothing to disclose.
Lukasz Wylezinski, PhD (Decode Health Inc)	Dr. Wylezinski has received personal compensation for serving as an employee of Decode Health. Dr. Wylezinski has stock in Decode Health. The institution of Dr. Wylezinski has received research support from Decode Health. Dr. Wylezinski has received intellectual property interests from a discovery or technology relating to health care.
Cheryl Sesler	Ms. Sesler has received personal compensation for serving as an employee of Decode Health, Inc.. Ms. Sesler has or had stock in Decode Health, Inc.
Mahboobeh Fereidan Esfahani, MD	Dr. Fereidan Esfahani has nothing to disclose.
Jessica A. Sagen, MA (Mayo Clinic)	Ms. Sagen has nothing to disclose.
Hannah Gardener, ScD (University of Miami)	Ms. Gardener has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Intersocietal Accreditation Commission. Ms. Gardener has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Ellipse Analytics. Ms. Gardener has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Baum Hedlund. Ms. Gardener has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant with A Green Slate Consulting.
Jacob L. McCauley (University of Miami)	Mr. McCauley has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Galatea Bio, Inc. Mr. McCauley has or had stock in Pacific Biosciences of California, Inc. . The institution of Mr. McCauley has received research support from NIH.
Alberto J. Caban-Martinez, DO, PhD	Dr. Caban-Martinez has nothing to disclose.
Roberta Brambilla, PhD	The institution of Dr. Brambilla has received research support from NIH. The institution of Dr. Brambilla has received research support from FISM. Dr. Brambilla has received intellectual property interests from a discovery or technology relating to health care. Dr. Brambilla has a non-compensated relationship as a Member of the Scientific Committee with FISM that is relevant to AAN interests or activities.
Lilyana M. Amezcua, MD, FAAN (USC)	Dr. Amezcua has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD serono. Dr. Amezcua has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Amezcua has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. Dr. Amezcua has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for genentech. The institution of Dr. Amezcua has received research support from National MS Society. The institution of Dr. Amezcua has received research support from Genentech. The institution of Dr. Amezcua has received research support from Bristol Myers Squibb Foundation. The institution of Dr. Amezcua has received research support from NIH NINDS. The institution of Dr. Amezcua has received research support from Sanofi/Genzyme. The institution of Dr. Amezcua has received research support from Alexion.
W. O. Tobin, PhD, MBBCh, BAO, FAAN (Mayo Clinic)	The institution of Dr. Tobin has received research support from Merck. The institution of Dr. Tobin has received research support from National Institutes of Health. Dr. Tobin has received publishing royalties from a publication relating to health care. Dr. Tobin has received personal compensation in the range of $0-$499 for serving as a Paid consulting and advisory activities with Mayo Clinic Platform_Accelerate.
Farren Briggs, PhD (University of Miami Miller School of Medicine)	The institution of Prof. Briggs has received research support from NIH.

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