Abstract Details

Title Relationship between Skin Pigmentation, HLA, Vitamin D Status and Pediatric-Onset Multiple Sclerosis

Topic Child Neurology and Developmental Neurology

Presentation(s) S19 - Child Neurology: Updates in Autism, Migraine, MS, and Stroke (4:36 PM-4:47 PM)

Poster/Presentation
Number 007

Background Multiple Sclerosis (MS) risk varies by race, vitamin D status, HLA-DRB1*15 genotype and geographic place of residence during childhood. Place of residence can affect ultraviolet radiation exposure, and consequently influence dermal pigmentation.

Objective To determine whether HLA-DRB1*15 status, 25-hydroxyvitamin D (25(OH)D) levels measured at baseline, and skin tone are associated with MS outcome in children with acquired demyelinating syndromes (ADS).

Design/Methods 259 children with incident ADS were enrolled in a multi-site prospective study in Toronto and Philadelphia (43°-51° latitude). Non-sun exposed upper inner arm melanin content was measured using the DSM II ColorMeter device. 25(OH)D concentrations were measured in serum obtained within 60 days of symptom onset and compared to lab-reported normative values. Vitamin D insufficiency was defined as [25(OH)D] less than 75 nmol/l (30 ng/dl). HLA-DRB1*15 alleles were quantified using allele-specific PCR amplification. Statistical analysis was performed using Spearman correlation models and Wilcoxon or Kruskal-Wallis tests as appropriate.

Results 68 children were diagnosed with MS, 191 remained monophasic (monoADS). 45.5% of MS children were HLA-DRB1*15 positive compared to 29.9% of monoADS children (p=0.03). Additionally, MS children had lower 25(OH)D levels (mean=45.4, SD=22.7) than monoADS children (mean=61.9, SD=29.2; p<0.0001) at baseline. Non-sun exposed skin tone measured in the upper inner arm did not differ between children diagnosed with MS (melanin index, mean=46.4, SD=12.3) and monoADS (mean=43.5, SD=8.1; p=0.61). Interestingly, 25(OH)D levels correlated with upper inner arm melanin index in the MS group (rho= -0.42, p=0.02), but not in children with monoADS (rho= -0.11, p=0.43).

Conclusions The association of vitamin D insufficiency with MS outcome in children with ADS appears to relate, in part, to skin pigmentation. Further work is required to delineate the complex interplay between dietary vitamin D ingestion, sun exposure and pigmentation of sun-exposed skin, seasonal vitamin D concentrations, and genetic influences of vitamin D pathways with MS risk.

Authors/Disclosures
Candice Dunn PRESENTER	No disclosure on file
Julia O'Mahony (The Hospital for Sick Children)	Ms. O'Mahony has nothing to disclose.
Heather Hanwell, PhD (Hospital for Sick Children)	No disclosure on file
E. Ann Yeh, MD, MA, FRCPC (Hosptial for Sick Children)	Dr. Yeh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Yeh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for PRIME. Dr. Yeh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Yeh has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Yeh has received research support from Biogen. The institution of Dr. Yeh has received research support from Stem Cell Network. The institution of Dr. Yeh has received research support from CIHR. The institution of Dr. Yeh has received research support from Ontario Institute for Regenerative Medicine. The institution of Dr. Yeh has received research support from National MS Society. The institution of Dr. Yeh has received research support from NIH. The institution of Dr. Yeh has received research support from SickKids Foundation. The institution of Dr. Yeh has received research support from CMSC. The institution of Dr. Yeh has received research support from MSSC.
	No disclosure on file
Amit Bar-Or, MD, FRCPC (University of Pennsylvania)	Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merk/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for cabaletta. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. The institution of Dr. Bar-Or has received research support from Novartis. The institution of Dr. Bar-Or has received research support from Biogen. The institution of Dr. Bar-Or has received research support from Roche/Genentech.
Brenda L. Banwell, MD, FAAN (Childrens Hospital of Philadelphia)	Dr. Banwell has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Banwell has received personal compensation in the range of $0-$499 for serving as a Consultant for UCB. Dr. Banwell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Banwell has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Banwell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Banwell has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Banwell has received research support from National MS Society. The institution of Dr. Banwell has received research support from NIH.