Multiple Sclerosis: Causes

Pathogenesis (disease development)

The exact mechanism of the development of multiple sclerosis (MS) is not yet fully understood. What seems certain is that the body’s immune system overreacts, targeting the myelin sheath and autoaggressively destroying (destroying) it. Myelin is a lipid-rich biomembrane that spirally surrounds and electrically insulates the axons (axial processes) of nerve cells. T and B cells play a central role in this process. In this process, T lymphocytes, which are activated in the periphery, first enter the CNS through the blood–brain barrier and trigger an autoimmune reaction against myelin. As a result of this inflammatory process, the blood–brain barrier also becomes permeable to B cells, which, once activated in the brain, secrete cytokines, increasing the destruction of the myelin sheath. The lesions are inflammatory infiltrates. These, in turn, lead to changes in the body’s immune defenses through IgG (immunoglobulin G) formation or cytokines (proteins that regulate cell growth and differentiation). Viral infections (see below) are considered possible triggers of multiple sclerosis. In addition to the above-mentioned factors, various studies also point to a genetic component (see “Biographical Causes” below). Two to three years before the diagnosis of multiple sclerosis (MS) is made, the following abnormalities can be detected in the blood of later patients: Compared with healthy individuals, vitamin D levels drop sharply during this period. At the same time, the strength of the antibody immune response against the Epstein-Barr virus (EBV) increases. A new detection test that can distinguish between two different types of human herpes virus (HHV-6) provides evidence that the long-suspected viral etiology of MS may be correct, that the disease can be caused by type HHV-6a along with EBV.

Etiology (Causes)

Biographic causes

• Genetic burden from parents, grandparents (approximately 10-15% of MS cases have a hereditary component)
  • Genetic risk depending on gene polymorphisms:
    • Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
      • Genes: ALK, CLEC16A, FAM69A, HLA-DRA, IL7R, RPL5.
      • SNP: rs3135388 in the HLA-DRA gene.
        • Allele constellation: CT (3.0-fold).
        • Allele constellation: TT (3.0-fold to 6.0-fold)
      • SNP: rs7577363 in the gene ALK
        • Allele constellation: AG (1.37-fold).
        • Allele constellation: AA (> 1.37-fold)
      • SNP: rs6604026 in the gene RPL5
        • Allele constellation: CT (1.15-fold).
        • Allele constellation: CC (> 1.15-fold)
      • SNP: rs6498169 in the CLEC16A gene.
        • Allele constellation: AG (1.14-fold).
        • Allele constellation: AA (> 1.14-fold)
      • SNP: rs7536563 in the FAM69A gene.
        • Allele constellation: AG (1.12-fold).
        • Allele constellation: AA (> 1.12-fold)
      • SNP: rs6897932 in the IL7R gene.
        • Allele constellation: CC (1.08-fold).
        • Allele constellation: CT (0.91-fold)
        • Allele constellation: TT (0.70-fold)
    • Four gene variants (SNPs) associated with low vitamin D levels are significantly associated with increased risk of multiple sclerosis
    • Monozygotic (identical) twin pairs: 75% of cases that one sibling has MS, but the other does not; causative epigenetic differences in immune cells of the blood (at 7 different positions, the genome of the twin siblings was methylated differently).
    • HLA-DRB1* 15 association
• Those born in April are 24% more likely to be affected than those born in November
• Gender – Women are affected by relapsing-remitting multiple sclerosis about three times more often than men.
• Hormonal factors – low 25-hydroxy vitamin D levels after birth.

Behavioral causes

• Nutrition
  • Consumption of animal fats and meat
  • High intake of saturated fatty acids (SFA).
  • High salt intake – (co)factor in the development of autoimmunity; is controversial.
  • Micronutrient deficiency (vital substances) – see prevention with micronutrients.
• Consumption of stimulants
  • Tobacco (smoking, passive smoking)
    • Characteristic HLA-DRB1* 15 + smoking (4.5-fold increased risk): + passive smoking (7.7-fold increased risk).
• Psycho-social situation
  • Stress – stressful events are discussed as risk factors.
• Overweight (BMI ≥ 25; obesity).
• “Lack of sunlight” (vitamin D) – prevalence for MS increases with distance from the equator, with the highest prevalence being 250 sufferers per 100,000 population in the north of Scotland.

Disease-related causes

• Infections with numerous viruses such as measles, herpes or Epstein-Barr virus (EBV).

Environmental pollution – intoxications (poisonings).

• Feature HLA-DRB1* 15 + occupational exposure to solvents (30-fold increased risk) (the diagnosis was made at a mean age of 34 years).