THE CCR5 DELETION MUTATION FAILS TO PROTECT AGAINST MULTIPLE-SCLEROSIS

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 bot h patients with MS and mice with EAE, and anti-MIP-1 alpha antibodies have been shown to prevent EAE. Recently, a common deletion mutation i n the gene for the major receptor for MIP-1 alpha, chemokine receptor 5 (CCR5) has been described. Homozygotes for the mutation fail to expr ess this receptor. Moreover, homozygotes are highly protected against HIV infection, this has potential implications for the cell entry of i nfectious agents in other multifactorial diseases where a viral compon ent may be involved. In view of these aspects, a group of 120 unrelate d Australian relapsing/remitting MS and 168 unrelated control subjects were screened for the CCR5 Delta 32 mutation. There was no significan t difference in the allele frequency of CCR5 Delta 32 gene between the MS patients (0.1125) and the control population (0.0921). The presenc e of two CCR5 Delta 32 homozygotes in the MS patients indicates that t he absence of CCR5 is not protective against MS. These data suggest th at CCR5 is not an essential component in MS expression, though this ma y be due to redundancy in the chemokine system where different chemoki ne receptors may substitute for CCR5 when it is absent. (C) American S ociety for Histocompatibility and Immunogenetics, 1997. Published by E lsevier Science Inc.