HLA genotypes and disease severityassessed by magnetic resonance imaging findings in patients withmultiple sclerosis

The objective of the study was to examine the relationshipbetween HLA genotypes and disease severity as measured by brainMRI quantitative markers of demyelinating and destructivepathology in patients with multiple sclerosis (MS). We studied100 patients with MS and 122 age, sex-, ethnic- andresidence-matched controls. The DNA extraction and the genomictyping (A, B, DRB1 and DQB1 loci) were obtained withsequence-specific oligonucleotide method, using a commerciallyavailable reversible line blot assay (INNO-LIPA). All patientsunderwent a 1.5 tesla MRI examination of the brain. Diseaseseverity was assessed by clinical (Expanded Disability StatusScale (EDSS)) and MRI (T2- and T1-lesion load (LL) and brainparenchymal fraction (BPF)) outcome measures. HLA-DQB1* 02 (OR19.9, 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, corrp< 0.0006), -DRB1*15 (OR 4.6, 95% C.I. 3.7–5.6, uncorrp= 0.0001, corr-p=0.006), and -DRB1*03 (OR3.9, 95% C. I. 3.2–4.8, uncorr-p=0.0001, corrp= 0.006) alleleswere associated with MS. T2-, T1-LL, BPF and EDSS were notsignificantly different according to the carrier status of theseHLA alleles. No differences were found in the ratios of diseaseseverity/disease duration according to the HLA car rier status.Multiple regression analysis showed that a higher T2-LL wasassociated 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 wasassociated 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 andcorr-R2=0.21, p=0.0002) alleles, whereas the BPF was predictedonly by the presence of DRB1*12 allele (uncorr-R2=0.24, p=0.002and corr-R2=0.20, p=0.004). The study findings suggest that someHLA alleles may predict the destructive pathological processesvisible on MRI. Since the size of the sample studied isrelatively small, further studies are needed to draw any firmconclusion about genotype/phenotype correlation in patients withMS.