Evaluation of IL-35, as a Possible Biomarker for Follow-Up after Therapy, in Chronic Human Schistosoma Infection

Abstract

The host response to helminth infections is characterized by systemic and tissue-related immune responses that play a crucial role in pathological diseases. Recently, experimental studies have highlighted the role of regulatory T (Tregs) and B (Bregs) cells with secreted cytokines as important markers in anti-schistosomiasis immunity. We investigated the serical levels of five cytokines (TNFα, IFN-γ, IL-4, IL-10 and IL-35) in pre- and post-treatment samples from chronic Schistosoma infected patients to identify potential serological markers during follow-up therapy. Interestingly, we highlighted an increased serum level of IL-35 in the pre-therapy samples (median 439 pg/mL for Schistosoma haematobium and 100.5 pg/mL for Schistsoma mansoni infected patients) compared to a control group (median 62 pg/mL and 58 pg/mL, respectively, p ≤ 0.05), and a significantly lower concentration in post-therapy samples (181 pg/mL for S. haematobium and 49.5 pg/mL for S. mansoni infected patients, p ≤ 0.05). The present study suggests the possible role of IL-35 as a novel serological biomarker in the evaluation of Schistosoma therapy follow-up.

Keywords: IL-35; Schistosoma haematobium; Schistosoma mansoni.

Figure 1

Cytokine concentrations in serum samples from pre-therapy (Pre-therapy SH) and post-therapy (Post-therapy SH) Schistosoma haematobium (SH) patients (n = 15) vs. healthy controls (CON Neg) (n = 9). Values are expressed as median and quartile ranges; significant differences were evaluated by the Kruskal–Wallis test plus Dunn’s test. (A) TNFα. * p ≤ 0.05 post-therapy vs. CON Neg; (B) IFNγ. * p ≤ 0.05 pre- and post-therapy vs. CON Neg; (C) IL-4. * p ≤ 0.05 post-therapy vs. CON Neg; (D) IL-10. * p ≤ 0.05 pre- and post-therapy vs. CON Neg.

Figure 2

Cytokine concentrations in serum samples from pre-therapy (Pre-therapy SM) and post-therapy (Post-therapy SM) Schistosoma mansoni (SM) patients (mono- and co-infected) (n = 16) vs. healthy controls (CON Neg) (n = 9). Values are expressed as median and quartile ranges; significant differences were evaluated by the Kruskal–Wallis test plus Dunn’s test. (A) TNFα. * p ≤ 0.05 pre-therapy vs. healthy control (mono- and co-infected); (B) IFN-γ. * p ≤ 0.05 pre-therapy vs. control and § p ≤ 0.05 post therapy vs. pre-therapy (mono-infected only); (C) IL-4. No significant differences found; (D) IL-10. * p ≤ 0.05 pre-therapy vs. control and § p ≤ 0.05 post-therapy vs. pre-therapy.

Figure 3

IL-35 cytokine concentrations in serum samples from Schistosoma haematobium (SH) (n = 15) and Schistosoma mansoni (SM) mono- and co-infected patients (n = 16) and healthy controls (CON neg) (n = 9) pre- and post-therapy. Values are expressed as median and quartile ranges; significant differences were evaluated by the Kruskal–Wallis test plus Dunn’s test. (A) * p ≤ 0.05 pre-therapy vs. control and § p ≤ 0.05 post-therapy v pre-therapy; (B) * p ≤ 0.05 pre-therapy vs. control (mono- and co-infected) and § p ≤ 0.05 post therapy vs. pre-therapy (mono- and co-infected).