The impact of HLA-DRB1 alleles in a Hellenic, Pediatric-Onset Multiple Sclerosis cohort: Implications on clinical and...

Area of Science:

• Immunogenetics
• Neurology
• Human Leukocyte Antigen (HLA) research

Background:

• Pediatric-Onset Multiple Sclerosis (POMS) pathogenesis involves complex genetic, hormonal, and environmental factors.
• Human Leukocyte Antigen (HLA) polymorphisms, particularly HLA-DRB1*15:01, are strongly associated with Multiple Sclerosis (MS) in Caucasian populations.
• Investigating HLA-DRB1 allele prevalence in Hellenic POMS cohorts can elucidate genetic contributions to disease.

Purpose of the Study:

• To determine the prevalence of HLA-DRB1 alleles in a Hellenic cohort of Pediatric-Onset Multiple Sclerosis (POMS) patients.
• To explore associations between specific HLA-DRB1 alleles and clinical/imaging features of POMS.
• To expand the understanding of HLA associations in the context of POMS.

Main Methods:

• Genotyping of HLA-DRB1 alleles was performed using a standard low-resolution sequence-specific oligonucleotide (SSO) technique.
• A cohort of 100 POMS patients, 168 Adult-Onset MS (AOMS) patients, and 246 Healthy Controls (HCs) were enrolled.
• Statistical analysis included frequency comparisons and odds ratio calculations with 95% confidence intervals.

Main Results:

• POMS patients showed a significantly increased frequency of HLA-DRB1*03 compared to HCs and AOMS patients (p=0.016 and p=0.034, respectively).
• Carriers of HLA-DRB1*03 had a reduced risk of brainstem lesion development (p=0.011).
• A lower frequency of HLA-DRB1*07 (p=0.017) and HLA-DRB1*11 (p=0.016) was observed in POMS patients compared to HCs.

Conclusions:

• The HLA-DRB1*03 allele is associated with an increased risk for POMS and a decreased risk for brainstem lesion development.
• HLA-DRB1*07 and HLA-DRB1*11 alleles demonstrate a protective role in POMS.
• These findings contribute to the understanding of HLA associations in Pediatric-Onset Multiple Sclerosis.