Multiple Sclerosis Research Repository

”HLA genotype as a marker of multiple sclerosis prognosis: A pilot study”: Andreas P. Lyasandropoulos 

-HLA class I alleles have been associated with either reduced (HLA-A*02:01, HLA-B*44:02) or increased (HLA-A*03, HLA-B*07) susceptibility to MS and the HLA-A*02:01 has been shown to drive the protective signal

-lower brain atrophy and T2 lesion volume were observed in HLA-B*044 positive patients, esp those who were HLA-DRB*15:01 negative

-an association between the HLA-DRB1*15:01 allele and a reduction in N-acetyl-aspartate concentrations within NAWM via HMR spectroscopy, an increase in WM T2 lesion volume by MRI, a reduction in normalized brain parenchymal volume and an impairment in cognitive functions measured by PASAT-3

-the association between the HLA genotypes and age at onset is probably driven by the HLA-DQB1*06:02-HLFA-DRB*15:01 and the HLA-DA1*01:01-LA-DRB*01:01 haplotypes

-the presence of the HLFA-DR2 haplotype (molecular designation HLA-DRB1*15:01 HLA-DA*01: 02, HLA-DQB1*06:02) also associated with a higher risk of developing clinically definite MS within 5 years in 178 patients with optic neuritis

-HLA-DR2 homozygotes were significantly less frequent in patients with mild or benign MS compared with patients having non-mild MS, suggesting that HLA-DR2 may act as a disease modifier

-in the Italian study, a higher T2 lesion load was associated with the presence of 

HLA-DRB*04 and HLA-B*07 and a higher T1 lesion load with the presence of HLA-B*07

 and HLA-DRB1*12

-HLA-DRB1*01 allele was detected in MS patients with a benign disease course and 

was missing in malignant MS patients, suggesting that this allele acts as a modifier of 

disease progression

-HLA-A*02 seemed to be associated with better prognosis; this effect was significant for 

EDSS, MSSS and new lesion count; the effect was close to significant for T25FW; the 

lower new lesion count in the group with HLA-A*02 did not remain significant after the 

Introduction of any of the covariates

-the effect of the HLA-A*02 allele was also evaluated in the subpopulation of patients with the HLA-DRB1*15 allele; only MSSS still showed a significant effect for protectiveness, while the annualized whole brain atrophy (annualized percentage of brain volume change) showed a significant negative impact of HLA-A*02 for the subpopulation that contained HLA-DRB*15.  Both effects remained significant in case any of the covariates was added

-patients with HLA-B*44 seemed to be more susceptible to MS progression; most clinical scores and MRI measurements pointed towards a negative effective of HLA-B*44 in terms of disease status and progression; however, none of these scores reached statistical significance; in case any of the covariates was included, a significant negative effect of the patients with HLA-B*44 was found for the 9HPT and the number of new lesions

-For the HLA-DQB*06 allele, no conclusive results were obtained as differences between 

the groups with and without HLA-DQB1*06

-Based on our data, the HLA-A*02 seemed to be associated with better prognosis in MS, 

which confirmed the effects found in literature

-patients with HLA-B*44 seemed more susceptible to MS progression