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Abstract Details

Assessing the Balance Between Effector and Regulatory T cell Subsets in Pediatric Multiple Sclerosis
Multiple Sclerosis
S55 - MS Basic Science (4:25 PM-4:36 PM)
006

We previously demonstrated in cross-sectional analysis that, on average, children with MS exhibited increased frequencies and pro-inflammatory responses of particular Teff subsets, and diminished Treg function such that the balance between the Teff/Treg was dysregulated relative to children with monoADS. Of interest was whether this measure of Teff/Treg imbalance was a stable feature, or fluctuated over time, potentially associated with disease activity.

To assess whether abnormalities in effector (Teff) and regulatory (Treg) T cells in children with pediatric-onset multiple sclerosis (MS) as compared to children with monophasic acquired demyelinating syndromes (monoADS), are a stable disease feature, or fluctuate over time.

Frequencies of CD4+CCR2+CCR5+ and CD8+CD161highTCR-Vα7.2+ MAIT Teff subsets, and the ratios of Teff to Treg (CD4+CD25hiCD127lowFOXP3+) cells, were serially assessed in children with MS and monoADS, prospectively followed as part of the Canadian/CHOP Pediatric Demyelinating Disease Study.

Children with MS (n=14) harbored increased frequencies of CD4+CCR2+CCR5+ and CD8+CD161highTCR-Vα7.2+ MAIT Teff cells (p=0.021, and p=0.008, respectively), yet deficient Treg suppressive capacity (p=0.041), including diminished capacity to suppress the implicated Teff (p=0.01), compared to children with monoADS (n=7). In turn, the implicated Teff of MS patients were relatively resistant to suppression by normal Tregs (p=0.008). An abnormal Teff/Treg ratio at the individual level best distinguished MS children from controls (p<0.001). In a subset of serially studied children (n=10), Teff/Treg ratios of the individual children were relatively stable over a 3-5 year period, whether they had MS or monoADS.

Abnormalities in the Teff/Treg ratios distinguish children with MS from children with monoADS. These ratios tend to be relatively stable over time consistent with an intrinsic property of chronic immune dysregulation, which does not seem to be related to clinical disease activity.

Authors/Disclosures
Ina Mexhitaj, PhD (Sanofi)
PRESENTER
No disclosure on file
No disclosure on file
Rui Li (McGill University) No disclosure on file
Julia O'Mahony (The Hospital for Sick Children) Ms. O'Mahony has nothing to disclose.
No disclosure on file
No disclosure on file
Craig S. Moore, PhD (Memorial University of Newfoundland) Dr. Moore has nothing to disclose.
Trina Johnson, MD No disclosure on file
Dessa Sadovnick, PhD (VCHA-UBC Hospital) No disclosure on file
No disclosure on file
Douglas L. Arnold, MD, FAAN (Montreal Neurological Institute, McGill Univ) Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Frequency Therapeutics. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shionogi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Xfacto communications. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Find therapeutics. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Idorsia. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kiniksa. Dr. Arnold has stock in NeuroRx.
Bruno Gran, MD, PhD (Nottingham University Hospitals) Dr. Gran has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gilead. Dr. Gran has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche UK. Dr. Gran has received publishing royalties from a publication relating to health care.
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.
Ruth-Ann Marrie, MD, PhD (University of Manitoba) The institution of Dr. Marrie has received research support from CIHR. The institution of Dr. Marrie has received research support from MS Canada. The institution of Dr. Marrie has received research support from National MS Society. The institution of Dr. Marrie has received research support from Crohn's and Colitis Canada. The institution of Dr. Marrie has received research support from US Department of Defense. The institution of Dr. Marrie has received research support from The Arthritis Society. The institution of Dr. Marrie has received research support from CMSC.
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.
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.