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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 acute phase proteins.Plasma levels of CRP, Haptoglobin, SAA and α-2 macroglobulin 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. Data are shown as scatter plots with the bar representing the geometric mean.
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ppat-1002749-g002: Filarial lymphedema is associated with elevated levels of acute phase proteins.Plasma levels of CRP, Haptoglobin, SAA and α-2 macroglobulin 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. Data are shown as scatter plots with the bar representing the geometric mean.

Mentions: To determine the association of acute phase proteins with filarial disease, we measured the plasma levels of CRP, haptoglobin, SAA, and α-2m in the four groups. As shown in figure 2, CP Ag+ had significantly higher levels of CRP (GM of 30.9 pg/ml in CP Ag+ vs. 4.11 in INF; P<0.0001), haptoglobin (GM of 555.9 pg/ml in CP Ag+ vs. 140.1 in INF; P<0.0001), SAA (GM of 196.7 pg/ml in CP Ag+ vs. 96.9 in INF; P = 0.0037), and α-2m (GM of 4383 pg/ml in CP Ag+ vs. 1923 pg/m in INF; P = 0.0003) in comparison to INF. Similarly, among those without evidence of active filarial infection (Ag−), those with CP had significantly higher levels of CRP in comparison to EN (GM of 14.5 pg/ml in CP Ag− vs.1.9 in EN; P<0.0001), indicating that elevated CRP levels might be more reflective of the secondary events associated with pathology than with active infection. Thus, filarial lymphedema with active infection is characterized by elevated levels of several acute phase proteins.


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 acute phase proteins.Plasma levels of CRP, Haptoglobin, SAA and α-2 macroglobulin 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. 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-g002: Filarial lymphedema is associated with elevated levels of acute phase proteins.Plasma levels of CRP, Haptoglobin, SAA and α-2 macroglobulin 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. Data are shown as scatter plots with the bar representing the geometric mean.
Mentions: To determine the association of acute phase proteins with filarial disease, we measured the plasma levels of CRP, haptoglobin, SAA, and α-2m in the four groups. As shown in figure 2, CP Ag+ had significantly higher levels of CRP (GM of 30.9 pg/ml in CP Ag+ vs. 4.11 in INF; P<0.0001), haptoglobin (GM of 555.9 pg/ml in CP Ag+ vs. 140.1 in INF; P<0.0001), SAA (GM of 196.7 pg/ml in CP Ag+ vs. 96.9 in INF; P = 0.0037), and α-2m (GM of 4383 pg/ml in CP Ag+ vs. 1923 pg/m in INF; P = 0.0003) in comparison to INF. Similarly, among those without evidence of active filarial infection (Ag−), those with CP had significantly higher levels of CRP in comparison to EN (GM of 14.5 pg/ml in CP Ag− vs.1.9 in EN; P<0.0001), indicating that elevated CRP levels might be more reflective of the secondary events associated with pathology than with active infection. Thus, filarial lymphedema with active infection is characterized by elevated levels of several acute phase proteins.

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