The HLA-Dw2 haplotype segregates closely with multiple sclerosis in multiplex families

Multiple sclerosis (MS) is associated with the HLA class II specificity Dw2, but the importance of its influence has been questioned, since sib-pair analysis has failed to show linkage with this haplotype. However, the use of 'identity by descent' (IBD) analysis may not be ideal, since it does not make use of the facts that (i) the Dw2-haplotype is the only haplotype with a confirmed role in MS, and (ii) it performs its influence in a dominant manner. We have investigated nine Swedish multiplex MS families. In eight of the families, the Dw2 haplotype occurred in MS patients. Within these families, Dw2 was shared by all 17 individuals with MS. In a compilation of 48 published multiplex MS families in which at least one patient carried Dw2, only three of 107 individuals with MS did not carry the Dw2 haplotype. This indicates that the Dw2 haplotype, when present in familial MS, may confer a stronger influence in MS susceptibility than generally recognized.