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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

Filarial lymphedema is associated with elevated levels of LPS.Plasma levels of LPS, LBP, EndoCAb and sCD14 from asymptomatic infected [INF] individuals; filarial lymphedema individuals with active infection [CP Ag+]; filarial lymphedema individuals without active infection [CP Ag−] and endemic normal [EN] individuals were measured by ELISA and immunoassays. Data are shown as scatter plots with the bar representing the geometric mean.
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ppat-1002749-g001: Filarial lymphedema is associated with elevated levels of LPS.Plasma levels of LPS, LBP, EndoCAb and sCD14 from asymptomatic infected [INF] individuals; filarial lymphedema individuals with active infection [CP Ag+]; filarial lymphedema individuals without active infection [CP Ag−] and endemic normal [EN] individuals were measured by ELISA and immunoassays. Data are shown as scatter plots with the bar representing the geometric mean.

Mentions: To determine the association of microbial translocation and related markers with filarial lymphedema, we measured the plasma levels of LPS, LPB, EndoCAb, and sCD14 in CP Ag+, INF, CP Ag−, and EN. As shown in figure 1, CP Ag+ had significantly higher levels of LPS (GM of 4.24 EU/ml in CP Ag+ vs. 0.10 in INF; P<0.0001 by Mann-Whitney) but not sCD14 or EndoCAb in comparison to INF. Conversely, CP Ag+ had significantly lower levels of LBP (GM of 306.2 ng/ml in CP Ag+ vs. 21658 in INF; P<0.0001) in comparison to INF. However, no significant differences were observed in the levels of all four circulating microbial or related products between CP Ag− and EN. In addition, we consistently observed an inverse association between LPS and LBP levels in the CP Ag+ group (r2 = 0.862; P<0.0001). Thus, filarial lymphedema with active infection is characterized by elevated levels of circulating LPS.


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)

Filarial lymphedema is associated with elevated levels of LPS.Plasma levels of LPS, LBP, EndoCAb and sCD14 from asymptomatic infected [INF] individuals; filarial lymphedema individuals with active infection [CP Ag+]; filarial lymphedema individuals without active infection [CP Ag−] and endemic normal [EN] individuals were measured by ELISA and immunoassays. Data are shown as scatter plots with the bar representing the geometric mean.
© Copyright Policy
Related In: Results  -  Collection

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

ppat-1002749-g001: Filarial lymphedema is associated with elevated levels of LPS.Plasma levels of LPS, LBP, EndoCAb and sCD14 from asymptomatic infected [INF] individuals; filarial lymphedema individuals with active infection [CP Ag+]; filarial lymphedema individuals without active infection [CP Ag−] and endemic normal [EN] individuals were measured by ELISA and immunoassays. Data are shown as scatter plots with the bar representing the geometric mean.
Mentions: To determine the association of microbial translocation and related markers with filarial lymphedema, we measured the plasma levels of LPS, LPB, EndoCAb, and sCD14 in CP Ag+, INF, CP Ag−, and EN. As shown in figure 1, CP Ag+ had significantly higher levels of LPS (GM of 4.24 EU/ml in CP Ag+ vs. 0.10 in INF; P<0.0001 by Mann-Whitney) but not sCD14 or EndoCAb in comparison to INF. Conversely, CP Ag+ had significantly lower levels of LBP (GM of 306.2 ng/ml in CP Ag+ vs. 21658 in INF; P<0.0001) in comparison to INF. However, no significant differences were observed in the levels of all four circulating microbial or related products between CP Ag− and EN. In addition, we consistently observed an inverse association between LPS and LBP levels in the CP Ag+ group (r2 = 0.862; P<0.0001). Thus, filarial lymphedema with active infection is characterized by elevated levels of circulating LPS.

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