Abstract

This is a case series study to evaluate immunological markers associated with schistosomiasis advanced fibrosis, including 69 patients from an endemic area from the State of Sergipe and from the Hepatology Service of the University Hospital in Sergipe, Brazil. Hepatic fibrosis was classified based on Niamey protocol for ultrasonography (US). Immune response to Schistosoma mansoni antigens was evaluated by stimulating peripheral blood mononuclear cells (PBMCs) from these patients with either adult worm (SWAP—10 μg/ml) or egg (SEA—10 μg/ml) antigens or purified protein derivative of turberculin (PPD—10 μg/ml) or phytohemagglutinin (PHA—1 μg/ml) for 72 h. The levels of IFN-γ, TNF-α, IL-5, IL-10, and IL-17 were measured in these supernatants by ELISA and IL-9 by Luminex. Single nucleotide polymorphisms in IL-17, IL10, and CD209 genes were genotyped using TaqMan probe by qPCR. Higher levels of IL-9, IL-10, and IL-17 were found in PBMC supernatants of patients with advanced hepatic fibrosis. Direct correlations were detected between IL-9 and IL-17 levels with US spleen sizes, portal vein diameters, and periportal thickening. The CD209 rs2287886 AG polymorphism patients produce higher IL-17 levels. Together, these data suggest a role of these cytokines in the immunopathogenesis of advanced fibrosis in human schistosomiasis.

Highlights

  • Schistosomiasis is an infectious and parasitic disease which affects about 240 million people in 78 countries and around 700 million people live in areas at risk from this infection [1]

  • There were no significant differences in the levels of IFN-g, TNF-a, and IL-5 in the peripheral blood mononuclear cells (PBMCs) supernatants stimulated with soluble egg antigen (SEA) and SWAP (Figures 1D–I)

  • The present study detects a predominance of IL-17 (Th17) and IL-9 (Th9) production in hepatosplenic patients with advanced fibrosis in PBMC cultures stimulated with S. mansoni antigens

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Summary

INTRODUCTION

Schistosomiasis is an infectious and parasitic disease which affects about 240 million people in 78 countries and around 700 million people live in areas at risk from this infection [1]. The understanding of the molecular mechanisms involved in the immunopathogenesis of this disease can have important implications for intervention strategies, mainly in immunoprophylaxis, in schistosomiasis and in other parasitic diseases [5, 17] He present study evaluates the cytokine profiles of Th1 (IFN-g, TNF-a), Th2/Treg (IL-5, IL-10), Th9 (IL-9), and Th17 (IL-17) in peripheral blood mononuclear cell (PBMC) supernatants stimulated with soluble egg (SEA) and adult worm (SWAP) antigens from patients with schistosomiasis with different stages of hepatic fibrosis and investigates whether SNPs in IL17A, IL10, and CD209 receptor [dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN)] are associated with this pathogenesis and influence the expression of IL-10 and IL-17 in this population

Ethics Statement
Study Design and Patient Selection
RESULTS
DISCUSSION
ETHICS STATEMENT

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