Multiple sclerosis and HLA genotypes: A possible influence on brain atrophy.

Area of Science:

• Neuroimmunology
• Genetics
• Radiology

Background:

• The strongest genetic determinant for multiple sclerosis (MS) is associated with human leukocyte antigen (HLA) class II DRB1 and DQB1 loci.
• Genetic predisposition plays a significant role in MS pathogenesis.

Purpose of the Study:

• To investigate the association between predisposing human leukocyte antigen (HLA) genotypes and the development of brain atrophy in multiple sclerosis (MS).
• To determine if specific HLA genotypes contribute to the rate of brain volume loss in MS patients.

Main Methods:

• Categorized 240 MS patients into high-risk (two predisposing haplotypes) and medium/low-risk (one or no predisposing haplotypes) HLA genotype groups.
• Utilized brain magnetic resonance imaging (MRI) with SIENAX to estimate white matter (WM), gray matter (GM), and whole brain (WB) volumes.
• Assessed longitudinal brain atrophy using SIENA in a subset of 60 patients.

Main Results:

• High-risk HLA genotypes were identified in 21% of patients.
• Multiple regression analysis revealed that high-risk HLA genotypes were significantly associated with reduced WB (p=0.02) and GM (p=0.03) volumes, independent of clinical MS features.
• Longitudinal analysis showed a greater brain volume loss (-0.79%) in the high-risk HLA genotype group compared to the low-risk group (-0.56%).

Conclusions:

• The findings suggest a significant influence of HLA genotype on the degree of whole brain and gray matter atrophy in multiple sclerosis (MS).
• Further research is warranted to validate these genetic associations and their clinical implications in MS.