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

Abstract

The objective of the study was to examine the relation- ship 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 pa- tients 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 under- went a 1.5 tesla MRI examination of the brain. Disease severity was assessed by clinical (Expanded Dis- ability Status Scale (EDSS)) and MRI (T2- and T1-lesion load (LL) and brain parenchymal fraction (BPF)) outcome measures. HLA- DQB1*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 de- structive 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 geno- type/phenotype correlation in patients with MS. I Key words multiple sclerosis · HLA · MRI 1100

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