Multiple sclerosis and HLA class II susceptibility and resistance genes

✍ Scribed by Dr. D. G. Haegert; M. Michaud; C. Schwab; G. S. Francis

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 826 KB
• Volume: 26
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.490260108

✦ Synopsis

Probes to the HLA class I1 genes DRP, DQP, and DQa were used to study DNA from unrelated Caucasian multiple sclerosis (MS) patients by sequential restriction fragment length polymorphism (RFLP) analysis in Taql restriction enzyme digests. Comparison of 104 patients and 108 controls, who were not matched for DR type, has identified for the first time a linked series of allele-specific RFLPs or allogenotypes which form an extended haplotype that is preferentially associated with MS. These allogenotypes include DRwlS or DR2(15); DQPlb, which corresponds at the DNA level to the DQwl(DQw6) serotype; a DQAl allogenotype termed DQalb; and a 2.2 kb DX (DQA2) allogenotype termed DXaU (DQA2U).

The role of HLA class I1 genes in susceptibility to MS was found to be complex. First, 23 of 104 MS patients showed DR-DQ linkages which were not observed in our control population. We suggest these anomalous associations may be important in the pathogenesis of M S . Second, homozygosity of a 2.0 kb DX (DQA2) gene, termed DXaJJ (DQA2L), showed a strong negative association with MS. DXaL (DQA2L) is in strong linkage disequilibrium with DR1, S(wl1) 7, and a subset of DR4, all of which also showed a negative association with M S . Since DXaL (DQA2L) does not code for any known product, DR1, S(11), 4, and 7 become candidates for disease resistance genes. Third, in EcoRl and EcoRV digests of DNA from both controls and patients homozygous for DQPlb a number of different RFLP patterns were identified and these RFLPs were associated with either relapsing-remitting or progressive MS. This suggests there may be HLA sequence differences between individuals bearing a particular class I1 allele and these may correlate with the clinical course of MS.