Immunological markers indicating the effectiveness of pharmacological treatment in human hydatid disease

The relation of interferon‐gamma (IFN‐γ), IL‐4, IL‐10 production and specific IgE, total IgG, IgG subclass expression to the effectiveness of pharmacological treatment in human hydatid disease (Echinococcus granulosus infection) was evaluated in 27 hydatid patients divided into four clinical groups according to their response to albendazole/mebendazole therapy (full, partial, low and non‐responders). After parasite antigen stimulation, peripheral blood mononuclear cells (PBMC) from full responders produced significantly more IFN‐γ (P= 0·038), significantly less IL‐4 (P= 0·001) and less IL‐10 than PBMC from non‐responders. PBMC from partial and low responders produced intermediate cytokine concentrations. ELISA determining immunoglobulin production showed that sera from all non‐responders had IgE and IgG4 antibodies, both regulated by IL‐4. In contrast to IgG4, IgE decreased rapidly in full responders. Full responders also showed the highest percentage of IgG3 reactions. Qualitative analysis of total IgG responses in hydatid patients’ sera determined by immunoblotting showed that binding profiles to hydatid cyst fluid antigen differed in the four groups of treated patients. Non‐responders had the highest percentage of reactions to all subunits of antigens 5 and B, and full responders had the highest percentage of reactions to antigen 5 alone. The high IFN‐γ production associated with a lack of IL‐4 and low IL‐10 production in the full responders, and vice versa the high IL‐4 and IL‐10 production associated with lack of or low IFN‐γ production in the non‐responders implies Th1 cell activation in protective immunity and Th2 cell activation in susceptibility to hydatid disease. IgE may be a useful marker of therapeutic success in hydatid patients with pretreatment specific IgE antibodies. IgG subclass responses and differential immunoglobulin subclass binding pattern to hydatid antigens may also be useful in the immunosurveillance of hydatid disease.

[1]  R. Riganò,et al.  In vitro production of cytokines by peripheral blood mononuclear cells from hydatid patients , 1995, Clinical and experimental immunology.

[2]  R. Riganò,et al.  Detection of antibodies against Echinococcus granulosus major antigens and their subunits by immunoblotting. , 1991, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[3]  E. Ottesen,et al.  IgG antibody subclasses in human filariasis. Differential subclass recognition of parasite antigens correlates with different clinical manifestations of infection. , 1987, Journal of immunology.

[4]  M. M. Bradford A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[5]  A. Aceti,et al.  IgG subclasses in human hydatid disease: prominence of the IgG4 response. , 1993, International archives of allergy and immunology.

[6]  S. Bombardieri,et al.  An evaluation of an agar gel diffusion test with crude and purified antigens in the diagnosis of hydatid disease. , 1974, Bulletin of the World Health Organization.

[7]  H. Wen,et al.  Immunoglobulin G subclass responses in human cystic and alveolar echinococcosis. , 1994, The American journal of tropical medicine and hygiene.

[8]  D. Heiner,et al.  Immunoglobulin E and G4 antibodies in cysticercosis , 1990, Journal of clinical microbiology.

[9]  A. Hightower,et al.  Guatemalan human onchocerciasis. II. Evidence for IgG3 involvement in acquired immunity to Onchocerca volvulus and identification of possible immune-associated antigens. , 1991, Journal of immunology.

[10]  J. F. Williams,et al.  Purification of lipoprotein antigens of Echinococcus granulosus from sheep hydatid fluid. , 1971, The American journal of tropical medicine and hygiene.

[11]  T. Nutman,et al.  IgE and IgG subclass regulation by IL-4 and IFN-gamma in human helminth infections. Assessment by B cell precursor frequencies. , 1993, Journal of immunology.

[12]  A. Teggi,et al.  Therapy of human hydatid disease with mebendazole and albendazole , 1993, Antimicrobial Agents and Chemotherapy.

[13]  J. F. Williams,et al.  Evaluation of purified lipoprotein antigens of Echinococcus granulosus in the immunodiagnosis of human infection. , 1971, The American journal of tropical medicine and hygiene.

[14]  Y. Sakiyama,et al.  Regulation of IgE and IgG4 synthesis in patients with hyper IgE syndrome. , 1990, Immunology.

[15]  J. D. Smyth,et al.  The Biology of Echinococcus and hydatid disease , 1986 .

[16]  G. Grau,et al.  Immune mechanisms in bacterial and parasitic diseases: protective immunity versus pathology. , 1991, Current opinion in immunology.

[17]  S. Pauluzzi,et al.  Post Operative Surveillance of Human Hydatidosis: Evaluation of Immunodiagnostic Tests , 1992, Pathology.

[18]  F. Boctor,et al.  IgG subclasses in human chronic schistosomiasis: over‐production of schistosome‐specific and non‐specific IgG4 , 1990, Clinical and experimental immunology.

[19]  G. Bahr,et al.  Diagnostic value of anti-arc 5 IgG antibody and analysis of the IgG subclasses in sera of patients with cystic hydatid disease. , 1990 .

[20]  M. Biggerstaff,et al.  ELISA detection of human IgG subclass antibodies to Streptococcus mutans. , 1986, Journal of immunological methods.

[21]  S. Romagnani Regulation and deregulation of human IgE synthesis. , 1990, Immunology today.

[22]  R. Van Ree,et al.  Differential expression of IgE and IgG4 specific antibody responses in asymptomatic and chronic human filariasis. , 1993, Journal of immunology.

[23]  T. Nutman,et al.  Cytokine regulation of antigen-driven immunoglobulin production in filarial parasite infections in humans. , 1990, The Journal of clinical investigation.

[24]  R. Coffman,et al.  Role of Cytokines and CD4+ T‐Cell Subsets in the Regulation of Parasite Immunity and Disease , 1989, Immunological reviews.