Different Th1/Th2 responses to Anisakis simplex are related to distinct clinical manifestations in sensitized patients

Anisakis simplex is a fish parasite capable of inducing inflammatory and allergic reactions in humans who eat raw or undercooked fish. The aim of this study was to characterize the T helper type 1 (Th1)/Th2 immune response to parasite crude (CE) and thermostable (TsE) extracts in A. simplex-sensitized patients. Cytokines were quantified by a multiplex flow cytometric method in short-term whole blood cultures. Higher concentrations of IL-2, IL-4 and IL-5, measured with the CE and TsE, were found in patients than in controls. Patients showing urticaria-angio-oedema or anaphylaxis (UA/A) had higher total and specific IgE levels than those with gastrointestinal symptoms (GI). The UA/A group showed high levels of IL-5 and IL-4 and low expression of IFN-γ than the GI group. The GI group had significantly higher IFN-γ/IL4 ratio than the UA/A group. Four patients with severe GI symptoms reporting a delayed skin test reaction had very low values of specific IgE to A. simplex and higher IFN-γ/IL4 ratios than that observed in other patients belonging to the GI group. This short-term whole blood test can be useful for immune response characterization in Anisakis infection and showed that heated parasite antigens are still capable of inducing cellular immune response in sensitized patients.