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

Abstract

SUMMARY 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.

Recent Advances in the Immunology and Serological Diagnosis of Echinococcosis

“…It is noteworthy that the increased production of IL-4 and IL-10 in hydatid patients (Bayraktar et al, 2005) corresponds with high levels of IgE and IgG4 (Rigano et al, 1995b), suggesting regulation by IL-4 of IgE and IgG4 responses (Rigano et al, 2001;Rigano et al, 1995b;King and Nutman, 1993). Patients with a primary infection have higher levels of IL-2, IFN-γ and IL-5.…”

“…T-cell lines from a patient with an inactive cyst had a Th1 profile, while T-cell lines derived from patients with active and transitional hydatid cysts had mixed Th1/Th2 and Th0 clones , indicating that Th1 lymphocytes contribute significantly to the inactive stage of hydatid disease, with Th2 lymphocytes being more important in the active and transitional stages. When CE patients were drug-treated with albendazole/mebendazole, a Th1 cytokine profile, rather than a Th2 profile, typically dominated, indicating that Th1 responses have a role in the process of cyst degeneration (Rigano et al, 1995b). An increased Th1-type cytokine IFN-γ response has been suggested as a marker for monitoring AE patient treatment (Dvoroznakova et al, 2004), whereas as measurement of serum IL-4 may be a useful marker for the follow up of patients with CE (Rigano et al, 1999b).…”

Diagnostic sensitivity of enzyme-linked immunosorbent assay for IgG in hydatid disease

“…In patients undergoing successful removal of hydatid cyst, the IgG4 subclass becomes negative soon after surgery and those with relapsing disease maintain high IgG4 titres on ELSIA. This suggests that IgG4 subclass is a good marker for hydatidosis follow-up [10].…”

IL-4 gene expression in adventitial layer (fibrous layer) of hepatic ovine and bovine hydatid cysts

“…Regarding the role of IL4 in hydatid cyst infection, it has been shown that in peripheral blood mononuclear from hydatid cyst patients stimulated with this parasite antigens, IL4 increased significantly (Rigano et al 1995a). Also a high level of IL4 has been reported in patients with chronic hydatid cyst (Rigano et al 1995b;Zhang et al 2003;Rigano et al 1996) Fibrous layer develops by host as a protective response to hydatid cyst. Expression of high level of IL4 in fibrous layer shows that this cytokine may play a key function in regulation of immune response in favor or against the parasite.…”