Multiple sclerosis risk genotypes correlate with an elevated cerebrospinal fluid level of the suggested prognostic marker CXCL13

• Published in: Multiple sclerosis Vol. 19; no. 7; pp. 863 - 870
• Main Authors: Lindén, M, Khademi, M, Lima Bomfim, I, Piehl, F, Jagodic, M, Kockum, I, Olsson, T
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.06.2013; Sage Publications; Sage Publications Ltd
• Subjects: Biological and medical sciences; Biomarkers - cerebrospinal fluid; Chemokine CXCL13 - cerebrospinal fluid; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Enzyme-Linked Immunosorbent Assay; Genetic Predisposition to Disease - genetics; Genotype; HLA-A Antigens - genetics; HLA-DRB1 Chains - genetics; Humans; Medical sciences; Medicin och hälsovetenskap; Multiple Sclerosis - cerebrospinal fluid; Multiple Sclerosis - genetics; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Polymorphism, Single Nucleotide; Prognosis; Risk Factors; Transcriptome; Biomarker; single nucleotide polymorphism; multiple sclerosis; cerebrospinal fluid; disease progression; CXCL13; genetic susceptibility; HLA; prognosis; HLA-System; Nervous system diseases; Multiple sclerosis; Prognosis; Genotype; Cerebrospinal fluid; Inflammatory disease; Central nervous system disease; Risk factor; Degenerative disease; Single nucleotide polymorphism
• ISSN: 1352-4585; 1477-0970; 1477-0970
• DOI: 10.1177/1352458512463482

Background: The mechanisms of multiple sclerosis (MS) pathogenesis are still largely unknown. The heterogeneity of disease manifestations make the prediction of prognosis and choice of appropriate treatment protocols challenging. Recently, increased cerebrospinal fluid (CSF) levels of the B-cell chemokine CXCL13 was proposed as a possible marker for a more severe disease course and conversion from clinically isolated syndrome (CIS) to relapsing–remitting MS (RRMS). Objective: To investigate whether there are genetic susceptibility variants in MS that correlate with the levels of CXCL13 present in the CSF of MS patients. Methods: We genotyped the human leukocyte antigens HLA-DRB1 and HLA-A, plus a panel of single nucleotide polymorphisms (SNPs) that have been associated with susceptibility to MS and then correlated the genotypes with the levels of CXCL13, as measured with ELISA in the CSF of a total of 663 patients with MS, CIS, other neurological diseases (OND) or OND with an inflammatory component (iOND). Results: Presence of the HLA-DRB1*15 and the MS risk genotypes for SNPs in the RGS1, IRF5 and OLIG3/TNFAIP3 gene regions correlated significantly with increased levels of CXCL13. Conclusion: Our results pointed towards a genetic predisposition for increased CXCL13 levels, which in MS patients correlates with the severity of the disease course. These findings encourage further investigation and replication, in an independent patient cohort.