Dataset Information

Association of genetic markers with CSF oligoclonal bands in multiple sclerosis patients.

ABSTRACT:

Objective

to explore the association between genetic markers and Oligoclonal Bands (OCB) in the Cerebro Spinal Fluid (CSF) of Italian Multiple Sclerosis patients.

Methods

We genotyped 1115 Italian patients for HLA-DRB1*15 and HLA-A*02. In a subset of 925 patients we tested association with 52 non-HLA SNPs associated with MS susceptibility and we calculated a weighted Genetic Risk Score. Finally, we performed a Genome Wide Association Study (GWAS) with OCB status on a subset of 562 patients. The best associated SNPs of the Italian GWAS were replicated in silico in Scandinavian and Belgian populations, and meta-analyzed.

Results

HLA-DRB1*15 is associated with OCB+: p?=?0.03, Odds Ratio (OR)?=?1.6, 95% Confidence Limits (CL)?=?1.1-2.4. None of the 52 non-HLA MS susceptibility loci was associated with OCB, except one SNP (rs2546890) near IL12B gene (OR: 1.45; 1.09-1.92). The weighted Genetic Risk Score mean was significantly (p?=?0.0008) higher in OCB+ (7.668) than in OCB- (7.412) patients. After meta-analysis on the three datasets (Italian, Scandinavian and Belgian) for the best associated signals resulted from the Italian GWAS, the strongest signal was a SNP (rs9320598) on chromosome 6q (p?=?9.4×10(-7)) outside the HLA region (65 Mb).

Discussion

genetic factors predispose to the development of OCB.

SUBMITTER: Leone MA

PROVIDER: S-EPMC3681825 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of genetic markers with CSF oligoclonal bands in multiple sclerosis patients.

Leone Maurizio A MA Barizzone Nadia N Esposito Federica F Lucenti Ausiliatrice A Harbo Hanne F HF Goris An A Kockum Ingrid I Oturai Annette Bang AB Celius Elisabeth Gulowsen EG Mero Inger L IL Dubois Bénédicte B Olsson Tomas T Søndergaard Helle Bach HB Cusi Daniele D Lupoli Sara S Andreassen Bettina Kulle BK Myhr Kjell-Morten KM Guerini Franca R FR Comi Giancarlo G Martinelli-Boneschi Filippo F D'Alfonso Sandra S

PloS one 20130613 6

<h4>Objective</h4>to explore the association between genetic markers and Oligoclonal Bands (OCB) in the Cerebro Spinal Fluid (CSF) of Italian Multiple Sclerosis patients.<h4>Methods</h4>We genotyped 1115 Italian patients for HLA-DRB1*15 and HLA-A*02. In a subset of 925 patients we tested association with 52 non-HLA SNPs associated with MS susceptibility and we calculated a weighted Genetic Risk Score. Finally, we performed a Genome Wide Association Study (GWAS) with OCB status on a subset of 562 ...[more]

PMID: 23785401

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Project description:Early diagnosis of multiple sclerosis (MS) relies on clinical evaluation, magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) analysis. Reliable biomarkers are needed to differentiate MS from other neurological conditions and to define the underlying pathogenesis. This study aimed to comprehensively profile immune activation biomarkers in the CSF of individuals with MS and explore distinct signatures between MS with and without oligoclonal bands (OCB). A total of 118 subjects, including relapsing-remitting MS with OCB (MS OCB+) (n = 58), without OCB (MS OCB-) (n = 24), and controls with other neurological diseases (OND) (n = 36), were included. CSF samples were analyzed by means of proximity extension assay (PEA) for quantifying 92 immune-related proteins. Neurofilament light chain (NfL), a marker of axonal damage, was also measured. Machine learning techniques were employed to identify biomarker panels differentiating MS with and without OCB from controls. Analyses were performed by splitting the cohort into a training and a validation set. CSF CD5 and IL-12B exhibited the highest discriminatory power in differentiating MS from controls. CSF MIP-1-alpha, CD5, CXCL10, CCL23 and CXCL9 were positively correlated with NfL. Multivariate models were developed to distinguish MS OCB+ and MS OCB- from controls. The model for MS OCB+ included IL-12B, CD5, CX3CL1, FGF-19, CST5, MCP-1 (91% sensitivity and 94% specificity in the training set, 81% sensitivity, and 94% specificity in the validation set). The model for MS OCB- included CX3CL1, CD5, NfL, CCL4 and OPG (87% sensitivity and 80% specificity in the training set, 56% sensitivity and 48% specificity in the validation set). Comprehensive immune profiling of CSF biomarkers in MS revealed distinct pathophysiological signatures associated with OCB status. The identified biomarker panels, enriched in T cell activation markers and immune mediators, hold promise for improved diagnostic accuracy and insights into MS pathogenesis.

Dataset Information

Association of genetic markers with CSF oligoclonal bands in multiple sclerosis patients.

Objective

Methods

Results

Discussion

Publications

Association of genetic markers with CSF oligoclonal bands in multiple sclerosis patients.

Similar Datasets

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