Авторы:N.N.Ozeretskovskaya1, O.G.Poletaeva1, V.P.Sergiev1, M.G.Isaguliants2, E.Linder2, T.A.Out3.

1 - E.I.Martsinovsky Institute of Medical Parasitology and Tropical Medicine, Moscow, Russia, 2 - The Swedish Institute of Infectious Diseases Control, Stockholm, Sweden, 3 - Academic Medical Center, Amsterdam, The Netherlands.

It took seventy years to establish that opistorchiasis in man is not a primary chronic disease but, as every other trematodosis, has an acute stage. The latter was revealed by discovery of rich gas and oil resources in West-Siberia in 60’s and mass migration of non-immune population to the area. In the host-parasite relationship established in the foci, the evolutionary pressure was exerted mostly on the host. The appearance of acute, in some cases severe, opisthorchiasis in migrants demonstrates that the northern population of O.felineus has not lost its virulence. Anyway we had described absence of acute stage of disease in aboriginals and half of the settlers of hyperendemic O.felineus foci, as well as transplacental transfer of parasite antigens in tolerant mothers, both supporting our concept of immunological tolerance to the agent. With immunologically tolerant host, there has been no need to parasite to lose pathogenecity. Whether the immunological tolerance is genetically stipulated is still unclear. In hyperendemic Hanti-Manssi region, 100% of aboriginals aged over ten have high stable level of egg output throughout entire life. This suggests existence of factors limiting the reinfection, such as «overpopulation», cholangiofibrosis, but primarily, specific immune responses. We characterised anti-parasite Th2 responses in patients with opistorchiasis as total and specific IgG, IgM, IgE antibodies and/or eosinophilia. Blood eosinophilia and total serum IgE and IgG4 content were determined in patients with acute, subacute (8) and chronic (2) opisthorchiasis. In acute phase, hypereosinophilia, normal IgG4 levels, and ten-fold increase in serum IgE coincided with general allergic reaction without organic pathology. One uncomplicated case was characterized by hypereosinophilia, and low content of both IgE and IgG4. Subacute case with acute gastroduodenitis was characterized by hypoeosinophilia, ten-fold elevated IgE and two-fold elevated IgG4 levels. Subacute case with hepatosplenomegaly coincided with blood eosinophilia, normal IgE and two-fold elevated IgG4. In another case, the content of both isotypes was low but patient was hypereosinophilic. Subacute case with jaundice, moderate liver enlargement with normal ALT/AST was characterized by blood eosinophilia, normal IgE, but elevated IgG4 level. Chronic case of opisthorchiasis resistant to prolonged chemotherapy with hexachlorparaxylol, with chronic gastroduodenitis and cholecystitis was characterized by normal blood eosinophil count, slightly elevated serum IgE and more than two-fold elevated IgG4. The uncomplicated hypereosinophilic cases of acute opisthorchiasis and cases with hepatosplenomegaly with normal IgE and IgG4 levels seem to belong to IL-4-independent allergic reactions. These data and our data on the cohort of patients with trichinellosis, toxocarosis and a matching group of allergics, points at correlation of potent early IgG4 production with development of organic and/or tissue pathology indicating the incompetence of anti-parasite immunity of the host. This corroborates the finding of early potent specific IgG4 production, inversely correlated to specific IgE, as a factor interfering with the mounting of protective immunity in shistosomiasis and lymphatic filariases. Next, we had screened patients with acute, subacute and chronic opisthorchiasis for IgG antibodies against paramyosin of Lumbricoidea (PM), peptides from paramyosins of Onchocerca volvulus, Echinococcus granulosus, and Schistosoma mansoni, recently shown by Loktev V.B. et al to be highly homologous to that of O. felineus. In parallel, sera were screened for reactivities against an aligned peptide from human *-cardiac myosin (*-cmp) known to induce experimental allergic myocarditis. All patients with acute and/or subacute opisthorchiasis reacted with PM. Acute patients with fever and hypereosinophilia (2), and subacute patients with hepatosplenomegaly (2), reacted with PM-derived peptides and cross-reacted with *-myosin peptide. Patients with moderate organic pathology reacted to PM and PM-derived peptides, but showed a lower level of cross-reactivity to *-cmp. Thus, cross-reactivity with *-myosin-derived peptide coincided with acuteness of general and/or local inflammation. This data indicates that production of IgG specific to paramyosin of the helminthes could provoke the inflammation, possibly through cross-reaction to host myosin or other *-helical structural proteins of the host, such as collagen, tropomyosin. In 40 practically healthy aboriginals of O. felineus foci, we found increased blood eosinophil content, elevated total serum IgM levels indicative of recent inflammatory responses, but no specific IgG antibodies; specific T-helper cell responses were low. Thus, our data support the concept that a benign Th2-dependent immune response to the parasite is exerted mostly through IgE, not IgG, antibody production. This correlates to the finding of S. mansoni-neutralizing antibodies belonging to IgE subclass. The Th2 responses mounted on the local level has yet to be evaluated.