title: Multiple sclerosis risk genotypes correlate with an elevated cerebrospinal fluid level of the suggested prognostic marker CXCL13.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet Stockholm, Sweden. magdalena.linden@ki.se
authors.forename: M
authors.initials: M
authors.lastname: Lindén
authors.forename: M
authors.initials: M
authors.lastname: Khademi
authors.forename: I
authors.initials: I
authors.lastname: Lima Bomfim
authors.forename: F
authors.initials: F
authors.lastname: Piehl
authors.forename: M
authors.initials: M
authors.lastname: Jagodic
authors.forename: I
authors.initials: I
authors.lastname: Kockum
authors.forename: T
authors.initials: T
authors.lastname: Olsson
mesh_terms: D015415:Biomarkers / Q000134:cerebrospinal fluid; D054382:Chemokine CXCL13 / Q000134:cerebrospinal fluid*; D004797:Enzyme-Linked Immunosorbent Assay; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D015234:HLA-A Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012307:Risk Factors; D059467:Transcriptome
chemical_list: D015415:Biomarkers; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D015234:HLA-A Antigens; D059811:HLA-DRB1 Chains