HLA (A-B-C and -DRB1) alleles and brain MRI changes in multiple sclerosis: a longitudinal study

Area of Science:

• Neuroimmunology
• Genetics of Autoimmune Diseases
• Medical Imaging in Neurology

Background:

• Major Histocompatibility Complex (MHC) alleles are implicated in multiple sclerosis (MS) susceptibility and disease course.
• Human Leukocyte Antigen (HLA) DRB1*1501 is a known risk factor for MS, but its role in modulating other HLA associations requires further investigation.

Purpose of the Study:

• To investigate the longitudinal impact of specific HLA class I/II alleles on MS clinical and radiological outcomes.
• To test the hypothesis that HLA DRB1*1501 modifies the association between other MHC alleles and magnetic resonance imaging (MRI) measures in MS patients.

Main Methods:

• Longitudinal study of 518 MS patients with HLA typing and serial brain MRI.
• Analysis of T2-weighted hyperintense lesion volume (T2LV) and brain parenchymal fraction (BPF) using linear regression.
• Stratification of analyses based on the presence or absence of HLA DRB1*1501.

Main Results:

• HLA DRB1*04 showed association with higher T2LV, significant only in the presence of HLA DRB1*1501.
• HLA DRB1*14 had a negative effect on T2LV in HLA DRB1*1501-negative individuals.
• HLA DRB1*10 demonstrated a protective effect on T2LV accrual when HLA DRB1*1501 was present.

Conclusions:

• Differential effects of HLA alleles on MS MRI outcomes are observed depending on the presence or absence of HLA DRB1*1501.
• These findings suggest potential interactions between HLA alleles in shaping the phenotypic expression of MS.
• Further research is warranted to confirm these associations and elucidate the underlying mechanisms.