The Role of Low-Resolution Classical HLA Class I and Class II Alleles in the Diagnosis, Clinical Features, and MRI Lesion Count of Multiple Sclerosis Patients

Background:Genetic susceptibility plays a central role in multiple sclerosis (MS), and combined evaluation of HLA class I and class II alleles may contribute to a better understanding of disease heterogeneity.Methods:This case–control study included 40 MS patients diagnosed according to the 2010 McDonald criteria and 40 healthy controls recruited from the Department of Neurology, Atatürk University Faculty of Medicine. Clinical parameters (disease duration, relapse characteristics, and EDSS scores) and MRI findings were recorded. HLA class I and class II typing was performed using the sequence-specific oligonucleotide (SSO) method, and statistical analyses were conducted using IBM SPSS Statistics (version 26.0). Frequencies of HLA class I and class II alleles and their combined genotypes were compared between groups.Results:The frequencies of HLA-A*03, HLA-A*32, and HLA-B*08 alleles were significantly higher in MS patients than in controls (p=0.0022). Significant differences were observed for several HLA class I–class II allele combinations, including B*52DR*15, B*08DQ*03, B*35DQ*02, C*03DR*04, C*07DR*11, and C*03DQ*03 (p=0.005). Carriers of HLA-C*03DR*04 and HLA-C*03DQ*03 exhibited a significantly higher number of cortical and juxtacortical lesions on MRI (p=0.0012 and p=0.0008, respectively). HLA-A*03 positivity was associated with increased infratentorial plaque burden (p=0.0040). Moreover, individuals carrying the combined HLA-C*03DR*04DQ*03 genotype demonstrated a significantly greater infratentorial lesion load (p=0.0012).Conclusion:Specific combinations of HLA class I and class II alleles are associated with MS susceptibility and distinct radiological phenotypes. HLA-based genetic profiling may therefore serve as a complementary tool for risk stratification and disease monitoring in MS.