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Circulating microbial products and acute phase proteins as markers of pathogenesis in lymphatic filarial disease.

Anuradha R, George PJ, Pavan Kumar N, Fay MP, Kumaraswami V, Nutman TB, Babu S - PLoS Pathog. (2012)

Bottom Line: Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients.Dysregulated host inflammatory responses leading to systemic immune activation are thought to play a central role in filarial disease pathogenesis.Thereafter, we tested for group effects among all the four groups using linear models on the log transformed responses of the markers.

View Article: PubMed Central - PubMed

Affiliation: National Institutes of Health, International Center for Excellence in Research, Chennai, India.

ABSTRACT
Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients. Dysregulated host inflammatory responses leading to systemic immune activation are thought to play a central role in filarial disease pathogenesis. We measured the plasma levels of microbial translocation markers, acute phase proteins, and inflammatory cytokines in individuals with chronic filarial pathology with (CP Ag+) or without (CP Ag-) active infection; with clinically asymptomatic infections (INF); and in those without infection (endemic normal [EN]). Comparisons between the two actively infected groups (CP Ag+ compared to INF) and those without active infection (CP Ag- compared to EN) were used preliminarily to identify markers of pathogenesis. Thereafter, we tested for group effects among all the four groups using linear models on the log transformed responses of the markers. Our data suggest that circulating levels of microbial translocation products (lipopolysaccharide and LPS-binding protein), acute phase proteins (haptoglobin and serum amyloid protein-A), and inflammatory cytokines (IL-1β, IL-12, and TNF-α) are associated with pathogenesis of disease in lymphatic filarial infection and implicate an important role for circulating microbial products and acute phase proteins.

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Related in: MedlinePlus

Heatmap depicting circulating microbial products, acute phase proteins and inflammatory cytokines in CP Ag+ individuals compared to EN, INF and CP Ag− individuals.Data (and scale) are log10 geometric mean fold change from EN for each of the analytes measured for each of the groups.
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ppat-1002749-g005: Heatmap depicting circulating microbial products, acute phase proteins and inflammatory cytokines in CP Ag+ individuals compared to EN, INF and CP Ag− individuals.Data (and scale) are log10 geometric mean fold change from EN for each of the analytes measured for each of the groups.

Mentions: We also compiled the comparative analysis of all the 12 parameters in the 4 groups of individuals as a heat map, depicting the log transformed data on a scale relative to EN. As shown in figure 5, CP Ag+ individuals exhibit a distinct biomarker signature characterized by elevated levels of LPS, acute phase proteins, and certain inflammatory cytokines compared with the other 3 groups (EN, INF, and CP Ag−), again reiterating the important association of these factors with pathogenesis of filarial pathology.


Circulating microbial products and acute phase proteins as markers of pathogenesis in lymphatic filarial disease.

Anuradha R, George PJ, Pavan Kumar N, Fay MP, Kumaraswami V, Nutman TB, Babu S - PLoS Pathog. (2012)

Heatmap depicting circulating microbial products, acute phase proteins and inflammatory cytokines in CP Ag+ individuals compared to EN, INF and CP Ag− individuals.Data (and scale) are log10 geometric mean fold change from EN for each of the analytes measured for each of the groups.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3369944&req=5

ppat-1002749-g005: Heatmap depicting circulating microbial products, acute phase proteins and inflammatory cytokines in CP Ag+ individuals compared to EN, INF and CP Ag− individuals.Data (and scale) are log10 geometric mean fold change from EN for each of the analytes measured for each of the groups.
Mentions: We also compiled the comparative analysis of all the 12 parameters in the 4 groups of individuals as a heat map, depicting the log transformed data on a scale relative to EN. As shown in figure 5, CP Ag+ individuals exhibit a distinct biomarker signature characterized by elevated levels of LPS, acute phase proteins, and certain inflammatory cytokines compared with the other 3 groups (EN, INF, and CP Ag−), again reiterating the important association of these factors with pathogenesis of filarial pathology.

Bottom Line: Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients.Dysregulated host inflammatory responses leading to systemic immune activation are thought to play a central role in filarial disease pathogenesis.Thereafter, we tested for group effects among all the four groups using linear models on the log transformed responses of the markers.

View Article: PubMed Central - PubMed

Affiliation: National Institutes of Health, International Center for Excellence in Research, Chennai, India.

ABSTRACT
Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients. Dysregulated host inflammatory responses leading to systemic immune activation are thought to play a central role in filarial disease pathogenesis. We measured the plasma levels of microbial translocation markers, acute phase proteins, and inflammatory cytokines in individuals with chronic filarial pathology with (CP Ag+) or without (CP Ag-) active infection; with clinically asymptomatic infections (INF); and in those without infection (endemic normal [EN]). Comparisons between the two actively infected groups (CP Ag+ compared to INF) and those without active infection (CP Ag- compared to EN) were used preliminarily to identify markers of pathogenesis. Thereafter, we tested for group effects among all the four groups using linear models on the log transformed responses of the markers. Our data suggest that circulating levels of microbial translocation products (lipopolysaccharide and LPS-binding protein), acute phase proteins (haptoglobin and serum amyloid protein-A), and inflammatory cytokines (IL-1β, IL-12, and TNF-α) are associated with pathogenesis of disease in lymphatic filarial infection and implicate an important role for circulating microbial products and acute phase proteins.

Show MeSH
Related in: MedlinePlus