Causes and risk factors in Multiple Sclerosis
Multiple sclerosis is a disease of unknown cause in which an as yet unidentified environmental factor is thought to trigger an abnormal immune response in a genetically susceptible individual.
Although this has not been fully established, MS is considered to be an autoimmune disease in which the immune system mistakenly recognizes one of the body's own proteins as foreign and mounts an immune response against it. This inflammatory "defensive" response ultimately damages the myelin sheath, the oligodendrocytes, and, secondarily, the axon.
Multiple sclerosis and the immune system
The immune system is the defence system against infections, tumours and other foreign elements. It is composed of different organs and tissues, cells, and proteins (antibodies). From among all the components of the immune system and in a very schematic way, we could say that the most important cells of this system are the white cells (leucocytes). These are divided into:
- Phagocytes. These are part of the innate immune system and act as the body's first line of defence against pathogens. They are cells capable of engulfing microorganisms and cellular debris (in general, any particles that are useless or harmful to the body) and internalising them in order to eliminate them.
- Lymphocytes. These are part of the adaptive immune system. They are responsible for generating a specific immune response to each foreign agent and for retaining immunological memory to prevent the same agent from causing disease again. Lymphocytes are divided into T cells and B cells, and they possess receptors that specifically recognise foreign substances (antigens) identified by the immune system.
In multiple sclerosis, there is initially an adaptive immune system response (lymphocytes). The genetic predisposition of the individual and the exposure to an unknown environmental factor triggers the onset of autoreactive (autoimmune) T lymphocytes.
After the activation of these lymphocytes, a cascade of events is produced that lead to the release of inflammatory mediators, harmful substances that damage the myelin, and the oligodendrocyte. This damage, in turn, activates the immune system again, amplifying this anomalous reaction.
Furthermore, the innate immune system (macrophages) also comes into action, activating phagocytosis mechanisms, either in parallel with or sequentially after the adaptive immune response. The cells of the central nervous system that are part of the innate immune system (microglia and astrocytes) alter the mitochondria —the structures responsible for producing cellular energy— through phagocytic mechanisms and the release of various substances. This damage impairs the normal function of nerve cells and leads to the loss of myelin (demyelination). This demyelination of neurons is partly responsible for the degeneration of nerve fibres (axons) and the neurodegenerative changes associated with the disease.
Risk factors in Multiple Sclerosis
Environmental factors in multiple sclerosis
North-south gradient. When further away from the equator, more frequent. White Caucasians, especially those who have ancestors from the north of Europe, have a higher risk than individuals of Asiatic, African, or native descent.
In immigrants, the presentation frequency differs from that of their parents. If someone emigrates before 15 years of age from a country with a low frequency to another of a high frequency, the risk is the same as the indigenous population.
High levels of vitamin D and sunlight, which would explain, at least in part, the north–south gradient.
Virus infections. Among the proposed causes, only infection with the Epstein–Barr virus has been consistently confirmed by epidemiological studies, particularly when infection occurs later in life and manifests as infectious mononucleosis.
Tobacco. It has not only been associated with the risk of developing it, but also with the risk of progressing to the secondary progressive form of the disease within a shorter period of time.
Genetic factors in multiple sclerosis
Several lines of evidence indicate that genetic factors play a role in the development of the disease:
- Certain ethnic groups appear to be relatively resistant to the disease.
- In the general population, the risk of developing the disease is 1–2 cases per 1,000 individuals, but this risk increases among first-degree relatives of an affected person and in children whose mother and father are both affected, although not in individuals adopted into families with an affected member.
- In monozygotic (identical) twins, if one twin has the disease, the risk that the other will also develop it is high (3 out of 10).
- There is an association with the major histocompatibility complex (MHC) class II. This, together with the more than 100 genetic variants that have been described, explains only slightly less than one-third of the genetic component of the disease.
Substantiated information by:
Published: 20 February 2018
Updated: 13 July 2026
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