Manypredisposing factors for multiple sclerosis (MS), such as HLA types and geomagnetic
fields have been described but the search for a single essential factor has
been like searching for the rainbow’s end. The most notable feature in the
epidemiology of MS in the Western world has been its rise from unknown to the
most prevalent disabling neurodegenerative disease of young adults. We suggest
that this may be largely or entirely attributable to societal changes that have
increasingly isolated populations from micro-organisms that form part of the
human microbiome and which are essential for an effective maturation of immune
defence mechanisms. This Darwinian explanation suggests a rational approach to
both prevention and treatment of MS, by substituting for the loss or absence of
factors that millions of years of evolution have led the immune system to
‘expect’ to encounter early in life.
BCG:
Bacille Calmette-Guérin; CDMS: Clinically Definite Multiple Sclerosis; CIS:
Clinically Isolated Syndrome; EBV: Epstein- Barr virus; HERV: Human Endogenous
Retrovirus; HLA: Human Leucocyte Antigen; IL: Interleukin; INF-α: Interferon
Alpha; MAIT: Mucosal-associated Invariant T Cells; MAMP: Microbe-associated
Molecular Pattern; MHC: Major Histocompatibility Complex; MRI: Magnetic
Resonance Imaging; MS: Multiple Sclerosis; TCR: T Cell Antigen Receptor; TNF-α:
Tumour Necrosis Factor Alpha; Treg: Regulatory T Cell; PRR: Pattern Recognition
Receptor; TLR: Toll-like Receptor; RA: Retinoic Acid.
Current
treatment strategies for multiple sclerosis (MS) are essentially empirical
because no single clear underlying cause of the disease has been determined.
Numerous genomic and environmental risk factors for MS have been described, but
problems of cause and effect remain unresolved. It has indeed been stated, with
considerable justification, that MS research is “low on fact, high on fiction” .
Although
there is a well-described genetically determined predisposition to MS, the
association is far from complete as, for example, the risk of an identical twin
sibling of an affected person developing MS is only 30%. Thus any genes
involved are likely to be of low penetration and influenced by the expression
of some or many other genes. Notwithstanding, a large number of genetic loci,
including many coding for HLA, have been determined and fine-mapped.
These studies have demonstrated a central role for the immune system in the
aetiopathogenesis of MS but the highly complex nature of the data will require
novel tools for their analysis before any unifying factor can be delineated.
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