HLA genotypes and disease severity assessed by magnetic resonance imaging findings in patients with multiple sclerosis

Robert Zivadinov, Laura Uxa, Tullio Zacchi, Davide Nasuelli, Maja Ukmar, Christina Furlan, Roberto Pozzi-Mucelli, Maria Antonietta Tommasi, Laura Locatelli, Sheila Ulivi, Alessio Bratina, Antonio Bosco, Attillio Grop, Giuseppe Cazzato, Marino Zorzon

Research output: Contribution to journalArticlepeer-review


The objective of the study was to examine the relationship between HLA genotypes and disease severity as measured by brain MRI quantitative markers of demyelinating and destructive pathology in patients with multiple sclerosis (MS). We studied 100 patients with MS and 122 age, sex-, ethnic- and residence-matched controls. The DNA extraction and the genomic typing (A, B, DRB1 and DQB1 loci) were obtained with sequence-specific oligonucleotide method, using a commercially available reversible line blot assay (INNO-LIPA). All patients underwent a 1.5 tesla MRI examination of the brain. Disease severity was assessed by clinical (Expanded Disability Status Scale (EDSS)) and MRI (T2- and T1-lesion load (LL) and brain parenchymal fraction (BPF)) outcome measures. HLADQB1*02 (OR 19.9, 95% C. I. 16.2-24.3, uncorrected (uncorr)- p <0.00001, corr-p <0.0006), -DQB1*03 (OR 16.8, 95% C. I. 13.6-20.5, uncorr-p <0.00001, corr-p <0.0006), -DRB1*15 (OR 4.6, 95% C. I. 3.7-5.6, uncorr-p = 0.0001, corr-p = 0.006), and -DRB1*03 (OR 3.9, 95 % C. I. 3.2-4.8, uncorr-p = 0.0001, corr-p = 0.006) alleles were associated with MS. T2-, T1-LL, BPF and EDSS were not significantly different according to the carrier status of these HLA alleles. No differences were found in the ratios of disease severity/disease duration according to the HLA carrier status. Multiple regression analysis showed that a higher T2-LL was associated with the presence of DRB1*04 (uncorr-R2 = 0.15, p = 0.006 and corr-R2 = 0.11, p = 0.025) and B7 alleles (uncorr-R2 = 0.08, p = 0.02 and corr-R2 = 0.07, p = 0.018), T1-LL was associated with B7 (uncorr-R2 = 0.30, p <0.0001 and corr-R2 = 0.27, p = 0.0001) and DRB1*12 (uncorr-R2 = 0.25, p <0.0001 and corr-R2 = 0.21, p = 0.0002) alleles, whereas the BPF was predicted only by the presence of DRB1*12 allele (uncorr-R2 = 0.24, p = 0.002 and corr-R2 = 0.20, p = 0.004). The study findings suggest that some HLA alleles may predict the destructive pathological processes visible on MRI. Since the size of the sample studied is relatively small, further studies are needed to draw any firm conclusion about genotype/phenotype correlation in patients with MS.

Original languageEnglish
Pages (from-to)1099-1106
Number of pages8
JournalJournal of Neurology
Issue number9
Publication statusPublished - Sep 1 2003


  • HLA
  • MRI
  • Multiple sclerosis

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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