As more studies are carried out into the relationship between parasitic infections and allergies, evidences are increasing in showing that some of the susceptibility loci in human genome are shared among parasitic diseases, but also with immunological disorders as allergy, suggesting that parasites may have played a role in driving the evolution of the immune system.
In this concerns, the planned proposal is aimed to investigate the relationship between human host-genetics and allergic diseases phenotypes, related to the zoonotic species of the marine ascarid nematode, Anisakis.
Thus, one objective of the proposal is to carry out a genetic epidemiological study on Italian patients showing various allergic disorders, associated to a IgE-hypersensitization to Anisakis.
The presence of susceptibility loci at the HLA, and other genes involved in the Th2 response in humans, possibly associated with IgE-hypersensitization in Anisakiasis, showing allergic diseases, will be investigated.
Further, because the evolutionary dynamics of the host-parasite coevolution processes can lead to the selection of most adaptive genotypes also in a parasite species, a second objective of the proposal is aimed to investigate, the possible occurrence of genotypes of Anisakis likely associated with different allergic disorders in humans. In particular, the existence of genetic variants (SNPs) in target genes coding for functional immunogenic proteins of zoonotic species of Anisakis that could be correlated to phenotypic conditions of anisakiasis, will be investigated.
Disentangling a potential host-parasite genetic architecture of the allergic manifestation associated with IgE-hypersensitivity to Anisakis, has never been approached. Data acquired on allele variants in the HLA genes systems, potentially associated to allergy and related traits, in anisakiasis in Italy, will represent an advance of the research to be carried out, around the "debate" on "Anisakis-allergy".
A genetic epidemiological investigation aimed to disentangling a potential host-genetic architecture of the allergic manifestation, associated with IgE-hypersensitivity to the marine ascarid parasite,
Anisakis, has never been investigated in Italian populations.
The hypothesis suggesting a possible role played by some geohelminths (i.e. Ascaris spp.), in driving the evolution of the immune system in selecting Th-2 upregulating variants in the HLA genes systems, that are responsible for allergy and related traits in actual human populations of Italy, would represent an advance of the research to be carried out, around the "debate" on "Anisakis-allergy".
The potential association between HLA-DRB1/DBQ1 alleles and genotypes, which will be detected in those patients with allergic symptomatology to Anisakis, will allow to identify a "genetic risk factor" in the human anisakiasis, especially in case of Gastro-allergic- anisakiasis (GAA) manifestation of the zoonosis. This would expose humans having those specific alleles/genotypes to encounter higher pathologic events during an Anisakis-infection, such as the anaphylactic shock. Similarly, a high allergic disease could be encountered with the large intake of fish-food found infected in the edible parts (fillets) with the larval parasites, by the patient having a genetic susceptibility to the disease.
The expected results will also clarify that the Anisakis tropomyosin recognition by IgE patients will be at higher occurrence in the Italian patients, likely associated with tropomyosin derived antigens from Ascaris spp. and other tropomyosins.
The results achieved will add knowledge for a correct human diagnosis of "Anisakis-allergy" to be carried out, taking into consideration other aspects of its onset in Italian patients.
Additionally, the potential finding of the correlation between alleles/genotypes in the genes coding for major antigens/allergens of the parasite Anisakis, will also contribute to enlarge the knowledge around the molecular mechanisms which are at the base of the host-parasite interaction.
The potential significant association between host genetic factors and IgE hypersensitization to Anisakis, will constitute a genetic data sets to be used in comparative analysis, in future investigations, performed on other Mediterranean populations (i.e. Spain, Croatia, Portugal, Morocco), from where also a high IgE-sensitization to the parasite Anisakis, has been reported. In addition, similarly, the genetic data sets with respect to those observed in other populations such as the Norwegian one, whose immune system have not speculated a long-term selective pressure by the Ascaris parasite, would add a support to the evolutionary-driven hypothesis.
The host-genetic perspective constitutes an innovative aspect of the research carried around the parasite-Anisakis, and a novel approach to be considered in this parasitic zoonosis.