Dataset Information

Human plasma lipid modulation in schistosomiasis mansoni depends on apolipoprotein E polymorphism.

ABSTRACT:

Background

Schistosomiasis mansoni is a parasitic liver disease, which causes several metabolic disturbances. Here, we evaluate the influence of Apolipoprotein E (APOE) gene polymorphism, a known modulator of lipid metabolism, on plasma lipid levels in patients with hepatosplenic schistosomiasis.

Methodology/principal findings

Blood samples were used for APOE genotyping and to measure total cholesterol (TC), LDL-C, HDL-C and triglycerides. Schistosomiasis patients had reduced TC, LDL-C and triglycerides (25%, 38% and 32% lower, respectively; P<0.0001) compared to control individuals, whereas HDL-C was increased (10% higher; P?=?0.0136). Frequency of the common alleles, ?2, ?3 and ?4, was similar (P?=?0.3568) between controls (n?=?108) and patients (n?=?84), implying that APOE genotype did not affect susceptibility to the advanced stage of schistosomiasis. Nevertheless, while patient TC and LDL-C levels were significantly reduced for each allele (except TC in ?2 patients), changes in HDL-C and triglycerides were noted only for the less common ?2 and ?4 alleles. The most striking finding, however, was that accepted regulation of plasma lipid levels by APOE genotype was disrupted by schistosomiasis. Thus, while ?2 controls had higher TC and LDL-C than ?3 carriers, these parameters were lower in ?2 versus ?3 patients. Similarly, the inverse relationship of TG levels in controls (?2>?3>?4) was absent in patients (?2 or ?4>?3), and the increase in HDL-C of ?2 or ?4 patients compared to ?3 patients was not seen in the control groups.

Conclusion/significance

We confirm that human schistosomiasis causes dyslipidemia and report for the first time that certain changes in plasma lipid and lipoprotein levels depend on APOE gene polymorphism. Importantly, we also concluded that S. mansoni disrupts the expected regulation of plasma lipids by the different ApoE isoforms. This finding suggests ways to identify new metabolic pathways affected by schistosomiasis and also potential molecular targets to treat associated morbidities.

SUBMITTER: Martins da Fonseca CS

PROVIDER: S-EPMC4106763 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Human plasma lipid modulation in schistosomiasis mansoni depends on apolipoprotein E polymorphism.

Martins da Fonseca Caíque Silveira CS Pimenta Filho Adenor Almeida AA dos Santos Bianka Santana BS da Silva César Augusto CA Domingues Ana Lúcia Coutinho AL Owen James Stuart JS Lima Vera Lúcia de Menezes VL

PloS one 20140722 7

<h4>Background</h4>Schistosomiasis mansoni is a parasitic liver disease, which causes several metabolic disturbances. Here, we evaluate the influence of Apolipoprotein E (APOE) gene polymorphism, a known modulator of lipid metabolism, on plasma lipid levels in patients with hepatosplenic schistosomiasis.<h4>Methodology/principal findings</h4>Blood samples were used for APOE genotyping and to measure total cholesterol (TC), LDL-C, HDL-C and triglycerides. Schistosomiasis patients had reduced TC, ...[more]

PMID: 25051269

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Project description:BackgroundSymptomatic acute schistosomiasis mansoni is a systemic hypersensitivity reaction against the migrating schistosomula and mature eggs after a primary infection. The mechanisms involved in the pathogenesis of acute schistosomiasis are not fully elucidated. Osteopontin has been implicated in granulomatous reactions and in acute hepatic injury. Our aims were to evaluate if osteopontin plays a role in acute Schistosoma mansoni infection in both human and experimentally infected mice and if circulating OPN levels could be a novel biomarker of this infection.Methodology/principal findingsSerum/plasma osteopontin levels were measured by ELISA in patients with acute (n = 28), hepatointestinal (n = 26), hepatosplenic (n = 39) schistosomiasis and in uninfected controls (n = 21). Liver osteopontin was assessed by immunohistochemistry in needle biopsies of 5 patients. Sera and hepatic osteopontin were quantified in the murine model of schistosomiasis mansoni during acute (7 and 8 weeks post infection, n = 10) and chronic (30 weeks post infection, n = 8) phase. Circulating osteopontin levels are increased in patients with acute schistosomiasis (p = 0.0001). The highest levels of OPN were observed during the peak of clinical symptoms (7-11 weeks post infection), returning to baseline level once the granulomas were modulated (>12 weeks post infection). The plasma levels in acute schistosomiasis were even higher than in hepatosplenic patients. The murine model mirrored the human disease. Macrophages were the major source of OPN in human and murine acute schistosomiasis, while the ductular reaction maintains OPN production in hepatosplenic disease. Soluble egg antigens from S. mansoni induced OPN expression in primary human kupffer cells.Conclusions/significanceS. mansoni egg antigens induce the production of OPN by macrophages in the necrotic-exudative granulomas characteristic of acute schistosomiasis mansoni. Circulating OPN levels are upregulated in human and murine acute schistosomiasis and could be a non-invasive biomarker of this form of disease.

Project description:BackgroundSchistosomiasis continues to be one of the most prevalent parasitic diseases in the world. Despite the existence of a highly effective antischistosome drug, the disease is spreading into new areas, and national control programs do not arrive to complete their tasks particularly in low endemic areas. The availability of a vaccine could represent an additional component to chemotherapy. Experimental vaccination studies are however necessary to identify parasite molecules that would serve as vaccine candidates. In the present work, C57BL/6 female mice were subcutaneously immunized with an n-butanol extract of the adult worm particulate membranous fraction (AWBE) and its protective effect against a S. mansoni challenge infection was evaluated.Methodology and findingsWater-saturated n-butanol release into the aqueous phase a set of membrane-associated (glyco)proteins that are variably recognized by antibodies in schistosome-infected patients; among the previously identified AWBE antigens there is Alkaline Phosphatase (SmAP) which has been associated with resistance to the infection in mice. As compared to control, a significantly lower number of perfuse parasites was obtained in the immunized/challenged mouse group (P<0.05, t test); and consequently, a lower number of eggs and granulomas (with reduced sizes), overall decreasing pathology. Immunized mice produced high levels of sera anti-AWBE IgG recognizing antigens of ∼190-, 130-, 98-, 47-, 28-23, 14-, and 9-kDa. The ∼130-kDa band (the AP dimer) exhibited in situ SmAP activity after addition of AP substrate and the activity was not apparently inhibited by host antibodies. A preliminary proteomic analysis of the 25-, 27-, and 28-kDa bands in the immunodominant 28-23 kDa region suggested that they are composed of actin.ConclusionsImmunization with AWBE induced the production of specific antibodies to various adult worm membrane molecules (including AP) and a partial (43%) protection against a challenging S. mansoni infection by mechanism(s) that still has to be elucidated.

Dataset Information

Human plasma lipid modulation in schistosomiasis mansoni depends on apolipoprotein E polymorphism.

Background

Methodology/principal findings

Conclusion/significance

Publications

Human plasma lipid modulation in schistosomiasis mansoni depends on apolipoprotein E polymorphism.

Similar Datasets

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