期刊
JOURNAL OF NEUROIMMUNOLOGY
卷 236, 期 1-2, 页码 76-80出版社
ELSEVIER
DOI: 10.1016/j.jneuroim.2011.04.011
关键词
Multiple sclerosis; HLA; Genetics; Clinically isolated syndromes; Progression; MRI
资金
- Biogen Idec
- Teva Neurosciences
- Questcor
- Genzyme
- EMD Serono
- National Multiple Sclerosis Society
- Teva Neuroscience
- Teva Pharmaceuticals
- Bracco
- Greatbatch
- Sanofi-Aventis
- Merck Serono
- Allergan
- Netezza
- Pfizer
- Jog for the Jake Foundation
- National Institutes of Health
- National Science Foundation
- Czech Ministry of Education [MSM 0021620849, IGA 1A8713-5/2005]
- Biogen Idec Inc.
- National Multiple Sclerosis Society [RG3743]
- Department of Defense [MS090122]
Objectives: The presence of MRI lesions at the first demyelinating event increases the risk of developing clinically definite multiple sclerosis (MS). The HL4 DRB1*1501 genotype is linked to MS susceptibility but its relationship to quantitative MRI parameters at the first demyelinating event has not been assessed. The objectives were to assess the associations between HLA DRB1*1501 status and magnetic resonance imaging (MRI) measures in clinically isolated syndromes (CIS) at the first demyelinating event. Methods: We genotyped 205 CIS patients (age: 29.0 +/- 7.7 years) enrolled in the Observational Study of Early Interferon beta 1-a Treatment in High Risk Subjects after CIS (SET study), a multi-center, clinical study of CIS for rs3135005, a single nucleotide polymorphism associated with HLA DRB1*1501 status. The inclusion criteria required 2 or more brain MRI lesions and the presence of two or more oligoclonal bands in cerebrospinal fluid. Clinical and MRI assessments were obtained within 4 months of the initial demyelinating event. Results: The frequency of HLA DRB1*1501 positivity was 102/205 (49.7%). HLA DR81*1501 positivity was associated with higher contrast-enhancing (CE) lesion number (p=0.002), higher CE-lesion volume (LV) (p<0.001) and exhibited a trend with higher T2-LV (p = 0.012). There was no evidence for significant associations of HLA DRB1*1501 positivity with disability, symptoms at CIS presentation, whole brain, white and gray matter atrophy. Conclusions: HLA DRB1*1501 positivity is associated with increased brain inflammatory processes at first clinical onset. However, the effect sizes of the HLA DRB1*1501 associations with MRI are modest, which potentially limits the clinical usefulness. (C) 2011 Elsevier B.V. All rights reserved.
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