The role of ST2 and ST2 genetic variants in schistosomiasis

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

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6 Scopus citations

Abstract

Background: Chronic schistosomiasis and its severe complication, periportal fibrosis, are characterized by a predominant T h 2 response. To date, specific single nucleotide polymorphisms in ST2 have been some of the most consistently associated genetic variants for asthma. Objective: We investigated the role of ST2 (a receptor for the T h 2 cytokine IL-33) in chronic and late-stage schistosomiasis caused by Schistosoma japonicum and the potential effect of ST2 genetic variants on stage of disease and ST2 expression. Methods: We recruited 947 adult participants (339 with end-stage schistosomiasis and liver cirrhosis, 307 with chronic infections without liver fibrosis, and 301 health controls) from a S japonicum-endemic area (Hubei, China). Six ST2 single nucleotide polymorphisms were genotyped. Serum soluble ST2 (sST2) was measured by ELISA, and ST2 expression in normal liver tissues, Hepatitis B virus-induced fibrotic liver tissues, and S japonicum-induced fibrotic liver tissues was measured by immunohistochemistry. Results: We found sST2 levels were significantly higher in the end-stage group (36.04 [95% CI, 33.85-38.37]) compared with chronic cases and controls (22.7 [95% CI, 22.0-23.4], P < 1E-10). In addition, S japonicum-induced fibrotic liver tissues showed increased ST2 staining compared with normal liver tissues (P = .0001). Markers rs12712135, rs1420101, and rs6543119 were strongly associated with sST2 levels (P = 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. Conclusions: We 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.

Original languageEnglish (US)
JournalJournal of Allergy and Clinical Immunology
DOIs
StateAccepted/In press - Jun 29 2016

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Keywords

  • Liver cirrhosis immunohistochemistry
  • Schistosoma japonicum
  • SST2
  • ST2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Long, X., Daya, M., Zhao, J., Rafaels, N., Liang, H., Potee, J., Campbell, M., Zhang, B., Araujo, M. I., Oliveira, R. R., Mathias, R. A., Gao, L., Ruczinski, I., Georas, S. N., Vercelli, D., Beaty, T. H., Barnes, K. C., Chen, X., & Chen, Q. (Accepted/In press). The role of ST2 and ST2 genetic variants in schistosomiasis. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2016.12.969