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Triggers of Autoimmune Disease
Cancers: Rarely, a cancer can cause an AI disease.
There are two methods:
- Immune system tumors:
Direct tumor of an immune organ such as the thymus
or bone marrow (i.e. athymoma orlymphoma). However,
AI disease is very rare from these disorders, so it
seems that despite their importance to the immune
system, a failure at these sites is not the only
problem required for AI disease to result.
Paraneoplastic autoimmune disorders: Though very
rare, there are a few types of autoimmune disease
that are caused by cancers of a different part of
the body. These are called "paraneoplastic"
autoimmune disorders. Examples include:
Cancer Associated Retinopathy (CAR): An
autoimmune reaction against the eye retina,
caused by some types of cancers, typically lung
The mechanism of paraneoplastic AI is believed
to be that the cancer causes a hidden antigen to be
shown to the immune system. This antigen is
attacked, but by coincidence, this antigen is also
at another body site (e.g. the retina), and the
immune system mistakenly attacks the retina as an
UV light may damage cells and release new antigens.
However, there are few examples of possible
relationships between radiation and autoimmunity.
Immune abnormalities: Because autoimmunity is
related to the immune system, various abnormalities of
the immune system have been considered as possible
triggers or causal factors.
- Cancers of immune
organs have been mentioned under cancers.
Thymus abnormalities: thymectomy: removal of the
thymus. Neonatal thymectomy causes oophoritis and
autoimmune gastritis in mice.
infections or inflammation: An infection causes
heightened immune response as a natural course. It is
therefore plausible that a chronic inflammation could
possibly cause autoimmunity, or if not actually cause,
at least provide an environment in which it would
- Cells: One strange method of causing autoimmunity is to
be injected with the cells of the body. This can sometimes
upset the balance of the immune system. Some examples
- Brain autoimmunity from rabies vaccinations, that
were once made from brain emulsions (modern rabies
vaccinations are not).
- Encephalitis in monkey brains after injection with
monkey brain cells.
Mitochondrial disorders: Not a general theory of AI, but
a possible factor in diabetes and MS. In diabetes,
mitochondrial failure might accumulate glutamate, leading to
an excess of GAD and thus causing anti-GAD antibodies
leading to diabetes. The genetic mitochondrial disorder
Leber's Hereditary Optic Neuropathy has been associated with
MS, but no clear link between mitochondria and MS has been
found as yet.
Triggering of Autoimmune Diseases
The methods whereby a particular trigger might cause the
conversion of the immune system into an autoimmune reaction.
- Tolerance theories: thymic deletion, clonal deletion,
negative selection, apoptosis, forbidden clone, anergy,
peripheral tolerance, etc. B-cells don't go to the thymus.
- Molecular mimicry: Difficulty getting experimental
confirmation in animal models. No known molecular mimics for
some substances (e.g. insulin/proinsulin, but there is for
islet cells and GAD).
- Epitope crossing