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Severson, Christopher

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Severson

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Christopher

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Severson, Christopher
Author's Publications: search.filters.isAuthorOfPublication.d2ada60d-3ca2-4f78-81ee-f2d301139a94

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    An expanded composite scale of MRI-defined disease severity in multiple sclerosis: MRDSS2
    (Lippincott Williams & Wilkins, 2014) Bakshi, Rohit; Neema, M; Tauhid, Shahamat; Healy, Brian C.; Glanz, Bonnie; Kim, Gloria; Miller, Jennifer; Berkowitz, Julia L.; Bove, Riley; Houtchens, Maria; Severson, Christopher; Stankiewicz, James; Stazzone, Lynn; Chitnis, Tanuja; Guttmann, Charles R.G.; Weiner, Howard; Ceccarelli, Antonia
    The objective of this study was to test a new version of the Magnetic Resonance Disease Severity Scale (MRDSS2), incorporating cerebral gray matter (GM) and spinal cord involvement from 3 T MRI, in modeling the relationship between MRI and physical disability or cognitive status in multiple sclerosis (MS). Fifty-five MS patients and 30 normal controls underwent high-resolution 3 T MRI. The patients had an Expanded Disability Status Scale score of 1.6±1.7 (mean±SD). The cerebral normalized GM fraction (GMF), the T2 lesion volume (T2LV), and the ratio of T1 hypointense LV to T2LV (T1/T2) were derived from brain images. Upper cervical spinal cord area (UCCA) was obtained from spinal cord images. A within-subject d-score (difference of MS from normal control) for each MRI component was calculated, equally weighted, and summed to form MRDSS2. With regard to the relationship between physical disability and MRDSS2 or its individual components, MRI–Expanded Disability Status Scale correlations were significant for MRDSS2 (r=0.33, P=0.013) and UCCA (r=−0.33, P=0.015), but not for GMF (P=0.198), T2LV (P=0.707), and T1/T2 (P=0.240). The inclusion of UCCA appeared to drive this MRI–disability relationship in MRDSS2. With regard to cognition, MRDSS2 showed a larger effect size (P=0.035) than its individual components [GMF (P=0.081), T2LV (P=0. 179), T1/T2 (P=0.043), and UCCA (P=0.818)] in comparing cognitively impaired with cognitively preserved patients (defined by the Minimal Assessment of Cognitive Function in MS). Both cerebral lesions (T1/T2) and atrophy (GMF) appeared to drive this relationship. We describe a new version of the MRDSS, which has been expanded to include cerebral GM and spinal cord involvement. MRDSS2 has concurrent validity with clinical status.
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    IL2RA Genetic Heterogeneity in Multiple Sclerosis and Type 1 Diabetes Susceptibility and Soluble Interleukin-2 Receptor Production
    (Public Library of Science, 2009) Maier, Lisa M.; Lowe, Christopher E.; Downes, Kate; Clark, Pamela M.; Walker, Neil; Aubin, Cristin; Oksenberg, Jorge R.; Hauser, Stephen L.; Compston, Alistair; Sawcer, Stephen; Wicker, Linda S.; Cooper, Jason S; Anderson, David E.; Severson, Christopher; Healy, Brian; The International Multiple Sclerosis Genetics Consortium; De Jager, Philip; Todd, John A.; Hafler, David
    Multiple sclerosis (MS) and type 1 diabetes (T1D) are organ-specific autoimmune disorders with significant heritability, part of which is conferred by shared alleles. For decades, the Human Leukocyte Antigen (HLA) complex was the only known susceptibility locus for both T1D and MS, but loci outside the HLA complex harboring risk alleles have been discovered and fully replicated. A genome-wide association scan for MS risk genes and candidate gene association studies have previously described the IL2RA gene region as a shared autoimmune locus. In order to investigate whether autoimmunity risk at IL2RA was due to distinct or shared alleles, we performed a genetic association study of three IL2RA variants in a DNA collection of up to 9,407 healthy controls, 2,420 MS, and 6,425 T1D subjects as well as 1,303 MS parent/child trios. Here, we report “allelic heterogeneity” at the IL2RA region between MS and T1D. We observe an allele associated with susceptibility to one disease and risk to the other, an allele that confers susceptibility to both diseases, and an allele that may only confer susceptibility to T1D. In addition, we tested the levels of soluble interleukin-2 receptor (sIL-2RA) in the serum from up to 69 healthy control subjects, 285 MS, and 1,317 T1D subjects. We demonstrate that multiple variants independently correlate with sIL-2RA levels.