title: The CCR5 deletion mutation fails to protect against multiple sclerosis.
abstract: Recent advances in the understanding and identification of chemokines and their receptors have provided evidence for their consideration as candidate loci with respect to genetic susceptibility/resistance to MS. Increased levels of the chemokine, macrophage inflammatory protein (MIP)-1 alpha, have been demonstrated in the cerebrospinal fluid of both patients with MS and mice with EAE, and anti-MIP-1 alpha antibodies have been shown to prevent EAE. Recently, a common deletion mutation in the gene for the major receptor for MIP-1 alpha, chemokine receptor 5 (CCR5) has been described. Homozygotes for the mutation fail to express this receptor. Moreover, homozygotes are highly protected against HIV infection this has potential implications for the cell entry of infectious agents in other multifactorial disease where a viral component may be involved. In view of these aspects, a group of 120 unrelated Australian relapsing remitting MS and 168 unrelated control subjects were screened for the CCR5 delta 32 mutation. There was no significant difference in the allele frequency of CCR5 delta 32 gene between the MS patients (0.1125) and the control population (0.0921). The presence of two CCR5 delta 32 homozygotes in the MS patients indicates that the absence of CCR5 is not protective against MS. These data suggest that CCR5 is not an essential component in MS expression, though this may be due to redundancy in the chemokine system where different chemokine receptors may substitute for CCR5 when it is absent.
authors.affiliation: Department of Clinical Immunology, Westmead Hospital, NSW, Australia. bruceb@westmed.wh.usyd.edu.au
authors.forename: B H
authors.initials: BH
authors.lastname: Bennetts
authors.forename: S M
authors.initials: SM
authors.lastname: Teutsch
authors.forename: M M
authors.initials: MM
authors.lastname: Buhler
authors.forename: R N
authors.initials: RN
authors.lastname: Heard
authors.forename: G J
authors.initials: GJ
authors.lastname: Stewart
mesh_terms: D019143:Evolution, Molecular; D017353:Gene Deletion; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D006720:Homozygote; D006801:Humans; D009103:Multiple Sclerosis / Q000276:immunology / Q000517:prevention & control*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D019713:Receptors, CCR5 / Q000235:genetics* / Q000276:immunology*
chemical_list: D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019713:Receptors, CCR5