Dataset Information

Identification of cytokeratin 18 as a biomarker of mouse and human hepatosplenic schistosomiasis.

ABSTRACT: Previously, we demonstrated unique protein expression patterns in 20-week-Schistosoma mansoni-infected CBA/J mice with moderate splenomegaly syndrome (MSS) or hypersplemomegaly syndrome (HSS). To better understand the development of severe pathology, we compared the two-dimensional differential in-gel electrophoresis (2D-DIGE) proteomic signatures of livers from uninfected mice and mice infected for 6, 8, 12, or 20 weeks and found significant changes in collagen isoforms, interleukin-2 (IL-2), cytokeratin 18, hydroxyproline, S. mansoni phosphoenolpyruvate carboxykinase, major urinary protein isoforms, and peroxiredoxin 6. Cytokeratin 18, hydroxyproline, and connective tissue growth factor (CTGF) were chosen for analysis in mouse and human sera using targeted biochemical assays. Consistent with the liver analysis, cytokeratin 18, CTGF, and hydroxyproline were significantly elevated in sera from mice with HSS compared to those from uninfected mice or mice with MSS. Moreover, cytokeratin 18 and CTGF were found to be markers for subjects with hepatosplenic and intestinal schistosomiasis, respectively, while serum hydroxyproline was a strong indicator of fibrosis for severe HS. These findings indicate that schistosome-associated changes to the liver can be detected in the serum and reveal the potential for cytokeratin 18 to be used as a diagnostic marker for early detection of hepatosplenic schistosomiasis.

SUBMITTER: Manivannan B

PROVIDER: S-EPMC3088153 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Identification of cytokeratin 18 as a biomarker of mouse and human hepatosplenic schistosomiasis.

Manivannan Bhagyashree B Rawson Pisana P Jordan T William TW Karanja Diana M S DM Mwinzi Pauline N M PN Secor William Evan WE La Flamme Anne Camille AC

Infection and immunity 20110228 5

Previously, we demonstrated unique protein expression patterns in 20-week-Schistosoma mansoni-infected CBA/J mice with moderate splenomegaly syndrome (MSS) or hypersplemomegaly syndrome (HSS). To better understand the development of severe pathology, we compared the two-dimensional differential in-gel electrophoresis (2D-DIGE) proteomic signatures of livers from uninfected mice and mice infected for 6, 8, 12, or 20 weeks and found significant changes in collagen isoforms, interleukin-2 (IL-2), c ...[more]

PMID: 21357724

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Project description:BackgroundHepatosplenic schistosomiasis (HSS) is a disease caused by chronic infection with Schistosma spp. parasites residing in the mesenteric plexus; portal hypertension causing gastrointestinal bleeding is the most dangerous complication of this condition. HSS requires complex clinical management, but no specific guidelines exist. We aimed to provide a comprehensive picture of consolidated findings and knowledge gaps on the diagnosis and treatment of HSS.Methodology/principal findingsWe reviewed relevant original publications including patients with HSS with no coinfections, published in the past 40 years, identified through MEDLINE and EMBASE databases. Treatment with praziquantel and HSS-associated pulmonary hypertension were not investigated. Of the included 60 publications, 13 focused on diagnostic aspects, 45 on therapeutic aspects, and 2 on both aspects. Results were summarized using effect direction plots. The most common diagnostic approaches to stratify patients based on the risk of variceal bleeding included the use of ultrasonography and platelet counts; on the contrary, evaluation and use of noninvasive tools to guide the choice of therapeutic interventions are lacking. Publications on therapeutic aspects included treatment with beta-blockers, local management of esophageal varices, surgical procedures, and transjugular intrahepatic portosystemic shunt. Overall, treatment approaches and measured outcomes were heterogeneous, and data on interventions for primary prevention of gastrointestinal bleeding and on the long-term follow-up after interventions were lacking.ConclusionsMost interventions have been developed on the basis of individual groups' experiences and almost never rigorously compared; furthermore, there is a lack of data regarding which parameters can guide the choice of intervention. These results highlight a dramatic need for the implementation of rigorous prospective studies with long-term follow-up in different settings to fill such fundamental gaps, still present for a disease affecting millions of patients worldwide.

Project description:BackgroundSchistosomiasis mansoni is an endemic parasitic disease and a public health problem in Northeast Brazil. In some patients, hepatic abnormalities lead to periportal fibrosis and result in the most severe clinical form, hepatosplenic schistosomiasis. This study aimed to evaluate whether abnormal blood coagulation and liver function tests in patients with hepatosplenic schistosomiasis (n = 55) correlate with the severity of their periportal fibrosis.Methodology/principal findingsBlood samples were used for liver function tests, hemogram and prothrombin time (International Normalized Ratio, INR). The blood coagulation factors (II, VII, VIII, IX and X), protein C and antithrombin IIa (ATIIa), plasminogen activator inhibitor 1 (PAI-1) and D-dimer were measured by photometry or enzyme linked immunosorbent assay. Hyperfibrinolysis was defined on the basis of PAI-1 levels and a D-dimer concentration greater than a standard cut-off of 483 ng/mL. Standard liver function tests were all abnormal in the patient group compared to healthy controls (n = 29), including raised serum transaminases (p<0.001) and lower levels of albumin (p = 0.0156). Platelet counts were 50% lower in patients, while for coagulation factors there was a 40% increase in the INR (p<0.001) and reduced levels of Factor VII and protein C in patients compared to the controls (both p<0.001). Additionally, patients with more advanced fibrosis (n = 38) had lower levels of protein C compared to those with only central fibrosis (p = 0.0124). The concentration of plasma PAI-1 in patients was one-third that of the control group (p<0.001), and D-dimer levels 2.2 times higher (p<0.001) with 13 of the 55 patients having levels above the cut-off.Conclusion/significanceThis study confirms that hemostatic abnormalities are associated with reduced liver function and increased liver fibrosis. Of note was the finding that a quarter of patients with hepatosplenic schistosomiasis and advanced periportal fibrosis have hyperfibrinolysis, as judged by excessive levels of D-dimer, which may predispose them to gastrointestinal bleeding.

Project description:BackgroundSchistosomiasis is endemic to several parts of the world. Among the species that affect humans, Schistosoma mansoni is one of the most common causes of illness. In regions where schistosomiasis mansoni is endemic, reinfection is responsible for the emergence of hepatosplenic schistosomiasis (HSS) with portal hypertension in about 10% of infected individuals. Regardless of its etiology, portal hypertension may bring about the formation of arteriovenous fistulas and pulmonary vascular dilation, thus constituting a pulmonary shunt and its presence has been associated with the occurrence of neurological complications. The objective of this study was to identify pulmonary shunt using TTCE in patients with HSS and esophageal varices, and to compare the abdominal ultrasound and endoscopy findings among patients with and without pulmonary shunt.Methodology/principal findingsIn this case series, a total of 461 patients with schistosomiasis mansoni were prospectively evaluated using abdominal ultrasound and endoscopy and 71 presented with HSS with esophageal varices. Fifty seven patients remained in the final analysis. The mean age of the patients was 55 ± 14 years, and 65% were female. Pulmonary shunts were observed in 19 (33.3%) patients. On comparing the groups with and without pulmonary shunt, no significant differences were observed in relation to the abdominal ultrasound and endoscopic findings. When comparing the two subgroups with pulmonary shunts (grade 1 vs grades 2 and 3), it was observed that the subgroup with shunt grades 2 and 3 presented with a significantly higher frequency of an enlarged splenic vein diameter (>0.9 cm), and an advanced pattern of periportal hepatic fibrosis (P = 0.041 and P = 0.005, respectively). None of the patients with pulmonary shunts had severe neurological complications.Conclusions/significanceOur findings suggest that in HSS with esophageal varices the pulmonary shunts may be present in higher grades and that in this condition it was associated with ultrasound findings compatible with advanced HSS.

Dataset Information

Identification of cytokeratin 18 as a biomarker of mouse and human hepatosplenic schistosomiasis.

Publications

Identification of cytokeratin 18 as a biomarker of mouse and human hepatosplenic schistosomiasis.

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