HLA associations with multiple sclerosis in Sicily and Malta

Area of Science:

• Immunogenetics
• Neurology
• Epidemiology

Background:

• Multiple sclerosis (MS) exhibits significant geographical variations in prevalence, notably between Sicily and Malta.
• In Northern Europe, MS is strongly associated with the Human Leukocyte Antigen (HLA)-DR2/Dw2 haplotype.
• The common HLA-A3-B7-DR2-Dw2 haplotype is frequently observed in Northern European MS patients.

Purpose of the Study:

• To investigate Human Leukocyte Antigen (HLA) Class I and II antigen frequencies and associations in Sicilian and Maltese populations.
• To determine if observed differences in HLA profiles could account for the disparity in multiple sclerosis (MS) prevalence between Sicily and Malta.

Main Methods:

• Analysis of HLA Class I (A, B) and Class II (DR, Dw) antigen frequencies in multiple sclerosis (MS) patients and control groups from Sicily and Malta.
• Comparison of HLA haplotype associations between the two islands and with previously established associations in Northern European populations.

Main Results:

• Sicilian MS patients showed an increased frequency of HLA-DR2 compared to controls, with most DR2-positive patients also being Dw2.
• Maltese individuals frequently carried HLA-DR2, but a significant portion lacked the Dw2 subtype, indicating diverse HLA Class II haplotype associations.
• Distinct differences in HLA-A, -B, and B-DR antigen associations were identified between the Sicilian and Maltese populations.

Conclusions:

• The genetic landscape, particularly HLA antigen associations, likely contributes to the differing prevalence rates of multiple sclerosis (MS) between Sicily and Malta.
• The specific HLA-DR2/Dw2 association common in Northern Europe may not be the sole determinant of MS susceptibility across different populations.