Hypocomplementaemic and normocomplementaemic multiple sclerosis. Genetic determinism and association with specific...

Area of Science:

• Immunogenetics
• Neuroimmunology
• Human Leukocyte Antigen (HLA) system

Background:

• Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system.
• The role of the complement system and human leukocyte antigen (HLA) associations in MS pathogenesis is not fully understood.
• Previous studies suggest potential links between immune dysregulation and MS.

Purpose of the Study:

• To investigate the correlation between complement component levels and HLA determinants in multiple sclerosis patients.
• To explore the potential genetic basis for complement abnormalities in MS families.
• To assess the frequency of infections in relation to complement levels and HLA associations in MS.

Main Methods:

• Assessed complement components (C3, Factor B, C4) and immunoglobulin levels (IgG, IgA, IgD, IgE) in 75 MS patients.
• Determined HLA-A and B determinants and measles antibody titres.
• Analyzed immunological values and HLA associations within 13 families, including siblings, parents, and children.

Main Results:

• A significant association was found between the HLA-B18 antigen and hypocomplementaemic MS patients (p < 0.001).
• Low C3 and/or Factor B levels were linked to HLA haplotypes, particularly those containing B18.
• Infections were more frequent in families with hypocomplementaemic MS, suggesting a genetic immunodeficiency.

Conclusions:

• A 'complement abnormality susceptibility gene' linked to HLA genes is postulated in MS.
• Findings suggest a genetic immunodeficiency affecting complement synthesis, associated with HLA determinants.
• A case of heterozygous C2 deficiency linked to HLA-A10, B18 supports the hypothesis of HLA-linked complement abnormalities in MS.