Review: Does the “Hygiene Hypothesis” Provide an Explanation for the High Prevalence of Multiple Sclerosis in Sardinia?

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Abstract
The “hygiene hypothesis” describes a hypothetical scenario in which the balance between TH1 (defending host against bacterial and viral infections) and TH2 (defending against parasitic infections) immune responses is pivotal and in which the consequence of reducing the infectious stressors during infancy is increased autoimmunity (TH1-mediated) and allergy (TH2-mediated). Many epidemiological observations confirm that allergic and autoimmune diseases are significantly increased in the “developed” countries and negatively associated with childhood infections. However, it has been recently revealed that immune elements associated with allergy are extensively involved also in the pathogenesis of autoimmune demyelination and that TH2- and TH1-mediated infections ameliorate the course of the disease confirming that the allergic root is also responsible for the escalation of autoimmune disorders, and both have a common immunological denominator. In the Italian island of Sardinia, MS and type-I diabetes frequencies have sharply increased in the last decades compared to other populations living in the same Mediterranean area. Initial observation led us to believe that environmental changes favoured the MS risk rise, thus sustaining the hygiene hypothesis. However, data on MS prevalence distribution in this territory suggest that other mechanisms than environment have also to be taken into great account. Our recent epidemiological studies reveal significant differences in the MS prevalence between rural and urban areas within the same province of Sassari but, contrarily to what expected from the hygiene hypothesis, MS prevalence is significantly higher in rural, genetically “archaic”, areas where the westernalization process has been less pronounced. On this basis we believe that, beside hygiene-related factors, genetics could represent a more relevant determinant of Sardinian high susceptibility to MS.