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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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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Schistosomiasis
Liver
Liver Cirrhosis
Single Nucleotide Polymorphism
Schistosoma japonicum
Hepatitis B virus
Brazil
China
Fibrosis
Asthma
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Staining and Labeling
Cytokines
Health
Infection
Serum

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., ... 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

The role of ST2 and ST2 genetic variants in schistosomiasis. / Long, Xin; Daya, Michelle; Zhao, Jianping; Rafaels, Nicholas; Liang, Huifang; Potee, Joseph; Campbell, Monica; Zhang, Bixiang; Araujo, Maria Ilma; Oliveira, Ricardo R.; Mathias, Rasika A.; Gao, Li; Ruczinski, Ingo; Georas, Steve N.; Vercelli, Donata; Beaty, Terri H.; Barnes, Kathleen C.; Chen, Xiaoping; Chen, Qian.

In: Journal of Allergy and Clinical Immunology, 29.06.2016.

Research output: Contribution to journalArticle

Long, X, Daya, M, Zhao, J, Rafaels, N, Liang, H, Potee, J, Campbell, M, Zhang, B, Araujo, MI, Oliveira, RR, Mathias, RA, Gao, L, Ruczinski, I, Georas, SN, Vercelli, D, Beaty, TH, Barnes, KC, Chen, X & Chen, Q 2016, '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
Long, Xin ; Daya, Michelle ; Zhao, Jianping ; Rafaels, Nicholas ; Liang, Huifang ; Potee, Joseph ; Campbell, Monica ; Zhang, Bixiang ; Araujo, Maria Ilma ; Oliveira, Ricardo R. ; Mathias, Rasika A. ; Gao, Li ; Ruczinski, Ingo ; Georas, Steve N. ; Vercelli, Donata ; Beaty, Terri H. ; Barnes, Kathleen C. ; Chen, Xiaoping ; Chen, Qian. / The role of ST2 and ST2 genetic variants in schistosomiasis. In: Journal of Allergy and Clinical Immunology. 2016.
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AU - Daya, Michelle

AU - Zhao, Jianping

AU - Rafaels, Nicholas

AU - Liang, Huifang

AU - Potee, Joseph

AU - Campbell, Monica

AU - Zhang, Bixiang

AU - Araujo, Maria Ilma

AU - Oliveira, Ricardo R.

AU - Mathias, Rasika A.

AU - Gao, Li

AU - Ruczinski, Ingo

AU - Georas, Steve N.

AU - Vercelli, Donata

AU - Beaty, Terri H.

AU - Barnes, Kathleen C.

AU - Chen, Xiaoping

AU - Chen, Qian

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N2 - 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.

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