ROLE OF PREDISPOSING AND PROTECTIVE HLA-DQA AND HLA-DQB ALLELES IN SARDINIAN MULTIPLE-SCLEROSIS

Objective.-To study the role of HLA genes in susceptibility and resistance to multiple sclerosis (MS) in Sardinian patients. To verify whether HLA-DQA and HLA-DQB genes differed between unrelated (MSU) and related (MSR) patients, and whether relapsing-remitting and chronic progressive forms of MS are immunogenetically distinct entities. Design.-Case-control study of HLA-DQA and HLA-DQB gene frequency. Setting.-All patients investigated were followed up by our MS referral centers. Patients.-The study involved 116 MSU patients, 67 of whom had a relapsing-remitting form (MSr), 28 of whom had a chronic progressive from-the-onset form (MSc), and 21 of whom had a benign form (MSb), 32 patients with MSR, 19 parents and 27 healthy siblings of patients with MSR, and 86 controls. Selection of patients was random, while control subjects came from families without known immunologic diseases. All patients had definite MS. Main Outcome Measure.-Statistical analysis of gene frequencies was conducted with the chi2 test with correction (P(c)) for the alleles investigated, as was decided before the study began. Results.-The DQA1*0301 allele was found to be increased in patients (MSU vs controls, P(c)=.008; patients with MSc vs controls, P(c)=.001; patients with MSR vs controls, P(c)=.02; and parents vs controls, P(c)=.04), while the DQA1 *0102 allele was found to be diminished in patients with MSr vs controls (P(c)=.001). Among the DQB genes, the DQB1*0502 allele was diminished in patients with MSr vs controls (P(c)=.04), while the sum of DQB1*0201 and *0302 alleles was significantly increased in patients with MSR vs controls (P(c)=.003). Conclusion.- Both HLA-DQA and HLA-DQB genes influence genetic susceptibility and resistance to MS. The roles of these genes differ in the various forms of MS. Patients with MSU and MSR both share HLA-DQA susceptibility genes.