Description | Oliveira, Ricardo Riccio. Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. aHepatic Surgery Center, bthe Clinical Study Center of Liver Surgery in Hubei
Province, and cthe Division of Gastroenterology and Hepatology, Tongji Hospital,
Tongji Medical College, Huazhong University of Science and Technology, Wuhan;
dthe Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School
of Medicine, and ethe Bloomberg School of Public Health, The Johns Hopkins University,
Baltimore; fthe Biomedical Informatics and Personalized Medicine, University of
Colorado School of Medicine, Aurora; gthe Arizona Respiratory Center, University of
Arizona, Tucson; hthe Department ofMedicine, University of Rochester Medical Center,
Rochester; ithe Servico de Imunologia, Hospital Universitario Professor Edgard
Santos, and jthe Instituto Goncalo Moniz, Fundacao Oswaldo Cruz - Bahia, Salvador - Xin Long, MD, PhD,a,b,d Michelle Daya, PhD,f Jianping Zhao, MD,a,b Nicholas Rafaels, MS,d Huifang Liang, MD, PhD,a,b
Joseph Potee, MS,d Monica Campbell, MS,d Bixiang Zhang, MD,a,b Maria Ilma Araujo, PhD,i Ricardo R. Oliveira, MS, PhD,j
Rasika A. Mathias, ScD,d Li Gao, MD, PhD,d Ingo Ruczinski, PhD,e Steve N. Georas, MD,h Donata Vercelli, MD,g
Terri H. Beaty, PhD,e Kathleen C. Barnes, PhD,d Xiaoping Chen, MD,a,b and Qian Chen, MD, PhD | pt_BR |
Abstract | Chronic schistosomiasis and its severe complication, periportal fibrosis, are characterized by a predominant Th2 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
TH2 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 endstage
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 endstage
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
(P5.0001). Markers rs12712135, rs1420101, and rs6543119 were
strongly associated with sST2 levels (P52E-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. | pt_BR |