Abstract Details

Title Co-Stimulatory Molecule CD40 Is Elevated in Type I Diabetes and Multiple Sclerosis Compared to Controls

Topic MS and Related Diseases

Presentation(s) P03 - (-)

Poster/Presentation
Number 233

Objective

Background BACKGROUND: Many patients have symptoms potentially referable to MS and nonspecific abnormalities on magnetic resonance imaging making diagnosis difficult. A blood test that distinguishes patients with MS from patients with non-MS disease would be very useful. We identified a subset of T cells that express the CD40 biomarker and have proven highly auto-aggressive in mouse models of MS. CD40 signaling produces pro-inflammatory cytokines which can influence T cell differentiation to Th17 cells or Th1 cells, potent inducers of autoimmune disease.

Design/Methods DESIGN/METHODS: Serum samples were collected from 121 treatment-naive patients with a clinically isolated sydrome (CIS) or new diagnosis MS at enrollment. Patient samples were collected at 6, 12 and 18 months. T-cells were isolated from peripheral blood by ficoll gradient. Cells were then stained and analyzed on Militenyi's Macsquant flow-cytometer. CD40 cells were reported as a percentage of the CD4 population above isotype controls. Comparison groups included those with T1D, T2D and healthy controls. All p values were determined using nonpaired t tests.

Results RESULTS: Percentage of cells expressing CD40 is elevated in patients who meet diagnostic criteria for MS (median 50%, mean 51%), including those with early forms of the disease (CIS) in comparison to healthy controls (p<0.0001). On average, the percentage of CD40 cells remained elevated 6 months and 12 months regardless of treatment (51.2%, 49.3%, respectively) or pregnancy (n=15).

Conclusions CONCLUSIONS: The expression of CD40 on CD4 cells is elevated in patients with MS in comparison to controls. CD40 may be a biomarker of disease activity in MS. Future studies will try to ascertain whether CD40 expression can distinguish MS from non-MS in all cases, the effect of immunotherapy on the expression of this biomarker, and whether it may be used prognostically.

Authors/Disclosures
Teri Schreiner, MD, MPH, FAAN (University of Colorado/ Children's Hospital of Colorado) PRESENTER	The institution of Dr. Schreiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CDC. Dr. Schreiner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. The institution of Dr. Schreiner has received research support from Roche Genentech.
Dan Waid	No disclosure on file
Jeffrey L. Saver, MD, FAAN (UCLA Health)	Dr. Saver has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medtronic. Dr. Saver has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Stryker. Dr. Saver has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cerenovus. Dr. Saver has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boehringer Ingelheim (prevention only). Dr. Saver 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 American Medical Association. Dr. Saver has received stock or an ownership interest from Rapid Medical.
	No disclosure on file
David H. Wagner, PhD (University of Colorado Anschutz Medical Campus)	No disclosure on file
John Corboy, MD, FAAN (U of Colorado School of Medicine)	Dr. Corboy has received personal compensation for serving as an employee of U of Coloado. Dr. Corboy has received personal compensation for serving as an employee of Rocky Mountain MS Center. Dr. Corboy has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Mylan. Dr. Corboy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squib. Dr. Corboy 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 AAN. Dr. Corboy 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 American Neurological Association. Dr. Corboy has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Mylan. The institution of Dr. Corboy has received research support from MedDay. The institution of Dr. Corboy has received research support from Novartis. The institution of Dr. Corboy has received research support from NMSS. The institution of Dr. Corboy has received research support from PCORI. The institution of Dr. Corboy has received research support from EMD Serono.

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