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The role of ST2 and ST2 genetic variants in schistosomiasis.

ABSTRACT: BACKGROUND: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 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.

SUBMITTER: Long X

PROVIDER: S-EPMC5550370 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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The role of ST2 and ST2 genetic variants in schistosomiasis.

Long Xin X Daya Michelle M Zhao Jianping J Rafaels Nicholas N Liang Huifang H Potee Joseph J Campbell Monica M Zhang Bixiang B Araujo Maria Ilma MI Oliveira Ricardo R RR Mathias Rasika A RA Gao Li L Ruczinski Ingo I Georas Steve N SN Vercelli Donata D Beaty Terri H TH Barnes Kathleen C KC Chen Xiaoping X Chen Qian Q

The Journal of allergy and clinical immunology 20170209 5

<h4>Background</h4>Chronic schistosomiasis and its severe complication, periportal fibrosis, are characterized by a predominant T<sub>h</sub>2 response. To date, specific single nucleotide polymorphisms in ST2 have been some of the most consistently associated genetic variants for asthma.<h4>Objective</h4>We investigated the role of ST2 (a receptor for the T<sub>h</sub>2 cytokine IL-33) in chronic and late-stage schistosomiasis caused by Schistosoma japonicum and the potential effect of ST2 gene ...[more]

PMID: 28189770

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Project description:BackgroundSchistosomiasis is a chronic parasitic disease, that affects over 207 million people and causes over 200,000 deaths annually, mainly in sub-Saharan Africa. Although many health measures have been carried out to limit parasite transmission, significant numbers of non-human primates such as Chlorocebus aethiops (Ch. aethiops) (vervet) and Papio anubis (baboon) are infected with S. mansoni, notably in Ethiopia, where they are expected to have potentially significant implications for transmission and control efforts.ObjectiveThe objective of this study was to assess and compare the genetic diversity and population structure of S. mansoni isolates from human and non-human primates free-ranging in close proximity to villages in selected endemic areas of Ethiopia.MethodsA cross-sectional study was conducted in three transmission sites: Bochesa, Kime and Fincha. A total of 2,356 S. mansoni miracidia were directly isolated from fecal specimens of 104 hosts (i.e. 60 human hosts and 44 non-human primates). We performed DNA extraction and PCR amplification using fourteen microsatellite loci.ResultsAt population scale we showed strong genetic structure between the three sample sites. At the definitive host scale, we observed that host factors can shape the genetic composition of parasite infra-populations. First, in male patients, we observed a positive link between parasite genetic diversity and the age of the patients. Second, we observed a difference in genetic diversity which was high in human males, medium in human females and low in non-human primates (NHPs). Finally, whatever the transmission site no genetic structure was observed between human and non-human primates, however, there appears to be little barriers, if any, host specificity of the S. mansoni populations with cross-host infections.ConclusionOccurrence of infection of a single host with multiple S. mansoni strains and inter- and intra-host genetic variations was observed. Substantial genetic diversity and gene flow across the S. mansoni population occurred at each site and non-human primates likely play a role in local transmission and maintenance of infection. Therefore, public health and wildlife professionals should work together to improve disease control and elimination strategies.

Dataset Information

The role of ST2 and ST2 genetic variants in schistosomiasis.

Publications

The role of ST2 and ST2 genetic variants in schistosomiasis.

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