The role of ST2 and ST2 genetic variants in schistosomiasis

Publication date: Available online 9 February 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Xin Long, Michelle Daya, Jianping Zhao, Nicholas Rafaels, Huifang Liang, Joseph Potee, Monica Campbell, Bixiang Zhang, Maria Ilma Araujo, Ricardo R. Oliveira, Rasika A. Mathias, Li Gao, Ingo Ruczinski, Steve N. Georas, Donata Vercelli, Terri H. Beaty, Kathleen C. Barnes, Xiaoping Chen, Qian Chen
BackgroundChronic schistosomiasis and its severe complication, periportal fibrosis, are characterized by a predominant Th2 response. To date, specific SNPs in ST2 have been some of the most consistently associated genetic variants for asthma.ObjectivesWe investigated the role of ST2 (a receptor for the Th2 cytokine IL-33) in chronic and late-stage schistosomiasis caused by S. japonicum, and the potential effect of ST2 genetic variants on stage of disease and ST2 expression.Methods947 adult participants (339 with end-stage schistosomiasis and liver cirrhosis, 307 with chronic infections without liver fibrosis, and 301 health controls) were recruited from a S. japonicum-endemic area (Hubei, China). Six ST2 SNPs were genotyped. Serum sST2 was measured by ELISA, and ST2 expression in normal liver tissues, HBV-induced fibrotic liver tissues and S. japonicum-induced fibrotic liver tissues was measured by immunohistochemistry.Results: sST2 levels were significantly higher in the end-stage group (36.04 [95 %CI 33.85;38.37]) compared to chronic cases and controls (22.7 [95% CI 22.0;23.4], p-value < 1E-10). In addition, S. japonicum-induced fibrotic liver tissues showed increased ST2 staining compared to normal liver tissues (p-value=0.0001). Markers rs12712135, rs1420101 and rs6543119 were strongly associated with sST2 levels (p-values 2E-10, 5E-05 and 6E-05 respectively), and these results were replicated in an independent cohort from Brazil living in a S. mansoni endemic region.ConclusionWe demonstrate for the first time that end-stage schistosomiasis is associated with elevated sST2 levels, and show that ST2 genetic variants are associated with sST2 levels in patients with schistosomiasis.

Teaser

ST2 mediates a Th2 response characteristic of both allergic and parasitic disease. We demonstrate that end-stage schistosomiasis is associated with sST2 levels and ST2 polymorphisms associated with asthma are associated with sST2 in schistosomiasis.


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