HLA‐DR2 and White Matter Lesion Distribution in MS

Human leukocyte antigen DR2 (HLA‐DR2) is a well‐established genetic risk factor for multiple sclerosis (MS). However, it is still unknown whether this factor is associated with a specific disease phenotype, and in particular, to a regional distribution of white matter (WM) lesion phenotype on magnetic resonance imaging (MRI). On a voxel‐by‐voxel basis, we analyzed the T1 and T2 MRI‐derived lesion maps of 50 patients with MS in order to determine the possible influence of HLA‐DR2 genotype on the lesional MRI pattern at early stages of the disease. HLA‐DR2 was present in 15 (30%) patients of our cohort. They displayed similar WM lesion distribution as the subjects without this factor. Thus, lesion distribution in MS seems to be independent of the DR2 genotype.

[1]  C. Shatz,et al.  Functional requirement for class I MHC in CNS development and plasticity. , 2000, Science.

[2]  Vincent Ferretti,et al.  A predominant role for the HLA class II region in the association of the MHC region with multiple sclerosis , 2005, Nature Genetics.

[3]  J. Haines,et al.  HLA-DR2 dose effect on susceptibility to multiple sclerosis and influence on disease course. , 2003, American journal of human genetics.

[4]  B. Weinshenker,et al.  Identifying disease modifying genes in multiple sclerosis , 2002, Journal of Neuroimmunology.

[5]  Carla J. Shatz,et al.  Immune signalling in neural development, synaptic plasticity and disease , 2004, Nature Reviews Neuroscience.

[6]  P. Goodfellow,et al.  The genetics of multiple sclerosis: principles, background and updated results of the United Kingdom systematic genome screen. , 1998, Brain : a journal of neurology.

[7]  C. Pozzilli,et al.  Predominant and stable T cell responses to regions of myelin basic protein can be detected in individual patients with multiple sclerosis , 1993, European journal of immunology.

[8]  J. Kurtzke Rating neurologic impairment in multiple sclerosis , 1983, Neurology.

[9]  B. Weinshenker,et al.  Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression. , 2006, Archives of neurology.

[10]  S. Hauser,et al.  The Neurobiology of Multiple Sclerosis: Genes, Inflammation, and Neurodegeneration , 2006, Neuron.

[11]  Silke Schmidt,et al.  Mapping multiple sclerosis susceptibility to the HLA-DR locus in African Americans. , 2004, American journal of human genetics.

[12]  X. Montalban,et al.  The HLA locus and multiple sclerosis in Spain. Role in disease susceptibility, clinical course and response to interferon-β , 2002, Journal of Neuroimmunology.

[13]  J. Libbey,et al.  Molecular Mimicry in Multiple Sclerosis , 2007, International Review of Neurobiology.

[14]  Karl J. Friston,et al.  A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains , 2001, NeuroImage.

[15]  S. Reingold,et al.  Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria” , 2005, Annals of neurology.

[16]  Joaquín Goñi,et al.  Fractal dimension and white matter changes in multiple sclerosis , 2007, NeuroImage.

[17]  J. Haines,et al.  Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group. , 1998, Human molecular genetics.

[18]  S. McQuaid,et al.  Absence of aquaporin-4 expression in lesions of neuromyelitis optica but increased expression in multiple sclerosis lesions and normal-appearing white matter , 2007, Acta Neuropathologica.

[19]  J. Parisi,et al.  Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis. , 2007, Brain : a journal of neurology.

[20]  Mara Cercignani,et al.  Regional gray matter atrophy in early primary progressive multiple sclerosis: a voxel-based morphometry study. , 2006, Archives of neurology.

[21]  Jonathan Taylor,et al.  Statistical mapping analysis of lesion location and neurological disability in multiple sclerosis: application to 452 patient data sets , 2003, NeuroImage.

[22]  S. Cole,et al.  Interaction between HLA-DR2 and abnormal brain MRI in optic neuritis and early MS. Optic Neuritis Study Group. , 2000, Neurology.

[23]  Thomas E. Nichols,et al.  Thresholding of Statistical Maps in Functional Neuroimaging Using the False Discovery Rate , 2002, NeuroImage.

[24]  S. Reingold,et al.  The Multiple Sclerosis Functional Composite measure (MSFC): an integrated approach to MS clinical outcome assessment , 1999, Multiple sclerosis.

[25]  S. Cole,et al.  Interaction between HLA-DR2 and abnormal brain MRI in optic neuritis and early MS , 2000, Neurology.

[26]  W. Matthews,et al.  McAlpine's multiple sclerosis , 1985 .

[27]  Pablo Villoslada,et al.  Heterogeneity at the HLA-DRB1 locus and risk for multiple sclerosis. , 2006, Human molecular genetics.