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Microbes & Immunity Infectious agents and autoimmune diseases

“hygiene hypothesis” and the healing effects of interferon-β women and men, in terms of immune system efficiency
(IFN-β), fit well into the framework of the new approach (besides boosting or suppressing it directly).
to the mechanism of autoimmune diseases, as explained in It has been observed that during pregnancy, women
the following paragraphs. are less susceptible to infections. As a result, fetuses are
4.1. Genetic predisposition better protected. This reduction of susceptibility could be
reasonably related to increased alertness of the immune
The role of genetic factors in autoimmune diseases is system, which, in turn, could favor the appearance or
indisputable. 5,44-46 Genetic predisposition to autoimmune exacerbation of autoimmune diseases. Nevertheless, this is
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diseases in general has been reported by Criswell et al. not always the case. For instance, remission of rheumatoid
and Li et al. Criswell et al. studied 265 multiplex arthritis during pregnancy has been extensively reported.
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families and found that at least two “core” autoimmune However, the causes are still unclear, and the proposed
diseases were present in each of these families. Li et al. conceptual model does not offer an explanation, either.
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analyzed the relationship between the polymorphisms of a
particular gene and susceptibility to autoimmune diseases. 4.3. Dietary habits
In addition, the genetic susceptibility of specific organs to The correlation of diet with certain autoimmune diseases is
autoimmune diseases has been reported by Owen et al. 49 statistically sound. Several explanations have been proposed
The findings, which relate autoimmune diseases to in the literature, such as industrial food processing and
genetic factors, fit well in the framework of the proposed food additive consumption. According to Lerner and
model. If the problem lies with the attacked organ, it could Matthias, 53(p479) “additives increase intestinal permeability by
be linked to its susceptibility to certain microbes, the breaching the integrity of tight junction paracellular transfer.
“imprint” of which renders it a target of the immune system. In fact, tight junction dysfunction is common in multiple
This explains the existence of many autoimmune diseases, autoimmune diseases.” Moreover, micronutrient deficiency,
each affecting different systems of the patients. Moreover, such as Vitamin D hypovitaminosis, has been related to the
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the presence of more than one disease in multiplex families onset and progression of autoimmune diseases through
can be due to their members’ infection by the same virus, impaired gut barrier function, due to deficient intestinal
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resulting in different autoimmune diseases. Even if genetic microbiota. Diet has also been related to the onset of
predisposition is linked to features of the immune system, autoimmune diseases through molecular mimicry. 55
these features could relate to increased ability to recognize Such observations fit very well in the framework of
pathogens’ imprints. the proposed model: unhealthy or unbalanced diet habits
render certain tissues more susceptible to infectious agents
4.2. Sex
and facilitate their alteration, making them targets of the
Women are generally more susceptible than men to many immune system.
autoimmune diseases (such as SLE, thyroiditis, and rheumatoid
arthritis), while they are more resistant to infections. A 4.4. Hygiene hypothesis
5,50
similar difference is exhibited in vaccine responses: women It is well-established that autoimmune diseases are
generally develop higher antibody responses and may much more widespread in developed countries than in
experience more adverse events than men. 51 developing ones. The well-known “hygiene hypothesis”
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The link between resistance to infections and directly correlates the decreasing incidence of infections in
susceptibility to autoimmune diseases can be explained developed countries with the increase of autoimmune (and
by the proposed model of the occurrence of autoimmune allergic) diseases.
diseases. Women have a more efficient immune system, This correlation, which is still an open research issue,
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which eventually protects them better from infections. can be explained in the framework of the proposed
However, this efficacy makes it easier for the immune mechanism of autoimmune diseases in the following way:
system to detect pathogens’ imprints and, thus, attack self- in regions with poor hygienic conditions and limited
cells, leading to more frequent occurrences of autoimmune access to medical treatment, many individuals succumb
responses. This explanation does not contradict findings to diseases that rarely cause deaths in developed countries.
relating sex-dependent differences with hormones (such However, in developed countries, some affected individuals,
as estrogens and progestins), genes on the X chromosome, despite receiving treatment, are not completely cured.
or environmental factors. The only difference is that, in The infectious agents may not be completely eradicated
the framework of the proposed conceptual model, these and continue to leave their “imprint” on cells, organs, or
factors can be considered as causes of differences between systems, rendering them immune system targets.

Volume 2 Issue 4 (2025) 21 doi: 10.36922/MI025100017