title: The chemokine receptor CCR5 Δ32 allele in natalizumab-treated multiple sclerosis.
abstract: OBJECTIVE
  The chemokine receptor CCR5 may be important for the recruitment of pathogenic T cells to the CNS in multiple sclerosis (MS). We hypothesized that this chemokine receptor might still be important for T-cell migration during treatment with anti-very late antigen (VLA)-4 antibody. We therefore analysed whether natalizumab-treated MS patients carrying the CCR5 Δ32 deletion allele, which results in reduced expression of CCR5 on the cell surface, had lower disease activity.
  
  
  METHODS
  CCR5 Δ32 was analysed in 212 natalizumab-treated MS patients.
  
  
  RESULTS
  CCR5 Δ32 status had no significant impact on the frequency of relapses 1 year prior to natalizumab treatment or during the first 48 weeks of treatment. The multiple sclerosis severity score (MSSS) was significantly lower at baseline in patients carrying CCR5 Δ32 (P = 0.031).
  
  
  CONCLUSIONS
  CCR5 Δ32 is not associated with lower disease activity in MS patients treated with natalizumab. We found lower MSSS scores in patients carrying CCR5 Δ32 compared with the remaining patients, which is consistent with previous studies reporting an association with a more favourable disease course. Further studies are, however, needed before the relationship between CCR5 Δ32 and disease activity in MS can be definitely established.
authors.affiliation: Department of Neurology, The Danish Multiple Sclerosis Center, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Møller
authors.forename: H B
authors.initials: HB
authors.lastname: Søndergaard
authors.forename: N
authors.initials: N
authors.lastname: Koch-Henriksen
authors.forename: P S
authors.initials: PS
authors.lastname: Sorensen
authors.forename: F
authors.initials: F
authors.lastname: Sellebjerg
authors.forename: A B
authors.initials: AB
authors.lastname: Oturai
mesh_terms: D000328:Adult; D000483:Alleles; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000235:genetics; D000069442:Natalizumab; D011446:Prospective Studies; D019713:Receptors, CCR5 / Q000235:genetics* / Q000502:physiology; D017384:Sequence Deletion; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C584933:CCR5 protein, human; D039041:Integrin alpha4beta1; D000069442:Natalizumab; D019713:Receptors, CCR5
keywords: demyelinating diseases; immunology; molecular genetics; multiple sclerosis