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Elevated soluble CD163 plasma levels are associated with disease severity in patients with hemorrhagic fever with renal syndrome.

Wang J, Guo W, Du H, Yu H, Jiang W, Zhu T, Bai X, Wang P - PLoS ONE (2014)

Bottom Line: The sCD163 plasma levels were measured using a sandwich ELISA, and the relationship between sCD163 and disease severity was analyzed.The results demonstrated that sCD163 plasma levels during the HFRS acute phase were significantly higher in patients than during the convalescent stage and the levels in the healthy controls (P<0.0001).The sCD163 plasma levels in the severe/critical group were higher than those in the mild/moderate group during the acute (P<0.0001).

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.

ABSTRACT

Background: Hantaan virus is a major zoonotic pathogen that causesing hemorrhagic fever with renal syndrome (HFRS). Although HFRS pathogenesis has not been entirely elucidated, the importance of host-related immune responses in HFRS pathogenesis has been widely recognized. CD163, a monocyte and macrophage-specific scavenger receptor that plays a vital function in the hosts can reduce inflammation, is shed during activation as soluble CD163 (sCD163). The aim of this study was to investigate the pathological significance of sCD163 in patients with HFRS.

Methods: Blood samples were collected from 81 hospitalized patients in Tangdu Hospital from October 2011 to January 2014 and from 15 healthy controls. The sCD163 plasma levels were measured using a sandwich ELISA, and the relationship between sCD163 and disease severity was analyzed. Furthermore, CD163 expression in 3 monocytes subset was analyzed by flow cytometry.

Results: The results demonstrated that sCD163 plasma levels during the HFRS acute phase were significantly higher in patients than during the convalescent stage and the levels in the healthy controls (P<0.0001). The sCD163 plasma levels in the severe/critical group were higher than those in the mild/moderate group during the acute (P<0.0001). A Spearman correlation analysis indicated that the sCD163 levels were positively correlated with white blood cell, serum creatine, blood urea nitrogen levels, while they were negatively correlated with blood platelet levels in the HFRS patients. The monocyte subsets were significantly altered during the acute stage. Though the CD163 expression levels within the monocyte subsets were increased during the acute stage, the highest CD163 expression level was observed in the CD14++CD16+ monocytes when compared with the other monocyte subsets.

Conclusion: sCD163 may be correlated with disease severity and the disease progression in HFRS patients; however, the underlying mechanisms should be explored further.

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Related in: MedlinePlus

The obvious changes in the soluble CD163 (sCD163) plasma levels in the different HFRS severity patient groups.(A) Comparison of plasma sCD163 levels at the different HFRS stages in the patients. Data were obtained from 145 plasma samples that were collected during the febrile/hypotensive (Febr/Hypo), oliguric (Olig), diuretic (Diur), and convalescent (Conv) HFRS phases in the patients and from 15 healthy subject plasma samples that were used as normal controls (NC). Significant differences were observed between the following stage comparisons: febrile/hypotensive or oliguric vs. NC (P<0.0001); febrile/hypotensive vs. diuretic or convalescent (P<0.0001); oliguric vs. diuretic (P = 0.035), oliguric vs. convalescent (P = 0.001); and diuretic vs. NC (P = 0.004). (B) The plasma sCD163 level changes in the acute (which included the febrile, hypotensive, and oliguric stages) and convalescent phase samples (which included the diuretic and convalescent stages) of the same patient in the different disease severity groups are represented. (C) The changes in the patient sCD163 plasma levels of the acute and convalescent phases when compared with the normal controls. (D) The changes in the sCD163 plasma levels during the acute phase and convalescent phases when compare with the normal controls in the different disease severity groups. (E) Comparison of the acute phase sCD163 levels between the mild/moderate and the severe/critical groups. The significance of the differences among the multiple groups was determined with the Kruskal-Wallis test. The significance of the differences between the two groups was determined with the Mann–Whitney U test. Black lines represent medians and the P values are plotted in each graph.
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pone-0112127-g001: The obvious changes in the soluble CD163 (sCD163) plasma levels in the different HFRS severity patient groups.(A) Comparison of plasma sCD163 levels at the different HFRS stages in the patients. Data were obtained from 145 plasma samples that were collected during the febrile/hypotensive (Febr/Hypo), oliguric (Olig), diuretic (Diur), and convalescent (Conv) HFRS phases in the patients and from 15 healthy subject plasma samples that were used as normal controls (NC). Significant differences were observed between the following stage comparisons: febrile/hypotensive or oliguric vs. NC (P<0.0001); febrile/hypotensive vs. diuretic or convalescent (P<0.0001); oliguric vs. diuretic (P = 0.035), oliguric vs. convalescent (P = 0.001); and diuretic vs. NC (P = 0.004). (B) The plasma sCD163 level changes in the acute (which included the febrile, hypotensive, and oliguric stages) and convalescent phase samples (which included the diuretic and convalescent stages) of the same patient in the different disease severity groups are represented. (C) The changes in the patient sCD163 plasma levels of the acute and convalescent phases when compared with the normal controls. (D) The changes in the sCD163 plasma levels during the acute phase and convalescent phases when compare with the normal controls in the different disease severity groups. (E) Comparison of the acute phase sCD163 levels between the mild/moderate and the severe/critical groups. The significance of the differences among the multiple groups was determined with the Kruskal-Wallis test. The significance of the differences between the two groups was determined with the Mann–Whitney U test. Black lines represent medians and the P values are plotted in each graph.

Mentions: The median sCD163 levels during the febrile/hypotensive, oliguric, diuretic, and convalescent stages, as well as in the normal controls, were 3.75 mg/l, 3.58 mg/l, 2.43 mg/l, 1.80 mg/l, and 0.81 mg/l, respectively. On the basis of the clinical disease course classification criteria, the acute phase comprised the febrile, hypotensive and oliguric stages, and the convalescent phase comprised the diuretic and convalescent stages [26]. During the acute phase, the sCD163 in the HFRS patient plasma samples was obviously higher than the levels observed in the normal controls (febrile/hypotensive or oliguric vs. NC, P <0.0001). The plasma sCD163 level in the HFRS patients decreased during the convalescent phase (febrile/hypotensive vs. diuretic or convalescent, P <0.0001; oliguric vs. convalescent, P = 0.001); however, it was still higher than the levels observed in the normal controls (diuretic vs. NC, P = 0.004) (Figure 1A). The plasma sCD163 levels in the patients with different disease severities displayed a similar change trend; however, a more distinct decline was observed in the severe/critical patient group (Figure 1B and 1D, P<0.0001). The sCD163 concentration in the acute phase was higher than the level that was observed during the convalescent phase in the HFRS patients (Figure 1C, P<0.001). The sCD163 concentration was also obviously higher during the acute and convalescent phases in the HFRS patients compared with those in the normal controls (P<0.0001), (Figure 1C and 1D). The sCD163 plasma levels in the severe/critical group were higher than those in the mild/moderate group during the acute (P<0.0001) (Figure 1E). The plasma sCD163 levels in the mild/moderate group were compared with those in the severe/critical group, and only 4 (13.7%) of the 29 mild/moderate group cases had plasma sCD163 levels that were over 4 mg/l, while 28 (60.8%) of the 46 severe/critical group cases had sCD163 levels that were over 4 mg/l (a 4.3-fold change between the high vs. mild/moderate groups). These results demonstrate that there was some kind of an association between the plasma sCD163 concentrations and the disease severity during the HFRS course.


Elevated soluble CD163 plasma levels are associated with disease severity in patients with hemorrhagic fever with renal syndrome.

Wang J, Guo W, Du H, Yu H, Jiang W, Zhu T, Bai X, Wang P - PLoS ONE (2014)

The obvious changes in the soluble CD163 (sCD163) plasma levels in the different HFRS severity patient groups.(A) Comparison of plasma sCD163 levels at the different HFRS stages in the patients. Data were obtained from 145 plasma samples that were collected during the febrile/hypotensive (Febr/Hypo), oliguric (Olig), diuretic (Diur), and convalescent (Conv) HFRS phases in the patients and from 15 healthy subject plasma samples that were used as normal controls (NC). Significant differences were observed between the following stage comparisons: febrile/hypotensive or oliguric vs. NC (P<0.0001); febrile/hypotensive vs. diuretic or convalescent (P<0.0001); oliguric vs. diuretic (P = 0.035), oliguric vs. convalescent (P = 0.001); and diuretic vs. NC (P = 0.004). (B) The plasma sCD163 level changes in the acute (which included the febrile, hypotensive, and oliguric stages) and convalescent phase samples (which included the diuretic and convalescent stages) of the same patient in the different disease severity groups are represented. (C) The changes in the patient sCD163 plasma levels of the acute and convalescent phases when compared with the normal controls. (D) The changes in the sCD163 plasma levels during the acute phase and convalescent phases when compare with the normal controls in the different disease severity groups. (E) Comparison of the acute phase sCD163 levels between the mild/moderate and the severe/critical groups. The significance of the differences among the multiple groups was determined with the Kruskal-Wallis test. The significance of the differences between the two groups was determined with the Mann–Whitney U test. Black lines represent medians and the P values are plotted in each graph.
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Related In: Results  -  Collection

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pone-0112127-g001: The obvious changes in the soluble CD163 (sCD163) plasma levels in the different HFRS severity patient groups.(A) Comparison of plasma sCD163 levels at the different HFRS stages in the patients. Data were obtained from 145 plasma samples that were collected during the febrile/hypotensive (Febr/Hypo), oliguric (Olig), diuretic (Diur), and convalescent (Conv) HFRS phases in the patients and from 15 healthy subject plasma samples that were used as normal controls (NC). Significant differences were observed between the following stage comparisons: febrile/hypotensive or oliguric vs. NC (P<0.0001); febrile/hypotensive vs. diuretic or convalescent (P<0.0001); oliguric vs. diuretic (P = 0.035), oliguric vs. convalescent (P = 0.001); and diuretic vs. NC (P = 0.004). (B) The plasma sCD163 level changes in the acute (which included the febrile, hypotensive, and oliguric stages) and convalescent phase samples (which included the diuretic and convalescent stages) of the same patient in the different disease severity groups are represented. (C) The changes in the patient sCD163 plasma levels of the acute and convalescent phases when compared with the normal controls. (D) The changes in the sCD163 plasma levels during the acute phase and convalescent phases when compare with the normal controls in the different disease severity groups. (E) Comparison of the acute phase sCD163 levels between the mild/moderate and the severe/critical groups. The significance of the differences among the multiple groups was determined with the Kruskal-Wallis test. The significance of the differences between the two groups was determined with the Mann–Whitney U test. Black lines represent medians and the P values are plotted in each graph.
Mentions: The median sCD163 levels during the febrile/hypotensive, oliguric, diuretic, and convalescent stages, as well as in the normal controls, were 3.75 mg/l, 3.58 mg/l, 2.43 mg/l, 1.80 mg/l, and 0.81 mg/l, respectively. On the basis of the clinical disease course classification criteria, the acute phase comprised the febrile, hypotensive and oliguric stages, and the convalescent phase comprised the diuretic and convalescent stages [26]. During the acute phase, the sCD163 in the HFRS patient plasma samples was obviously higher than the levels observed in the normal controls (febrile/hypotensive or oliguric vs. NC, P <0.0001). The plasma sCD163 level in the HFRS patients decreased during the convalescent phase (febrile/hypotensive vs. diuretic or convalescent, P <0.0001; oliguric vs. convalescent, P = 0.001); however, it was still higher than the levels observed in the normal controls (diuretic vs. NC, P = 0.004) (Figure 1A). The plasma sCD163 levels in the patients with different disease severities displayed a similar change trend; however, a more distinct decline was observed in the severe/critical patient group (Figure 1B and 1D, P<0.0001). The sCD163 concentration in the acute phase was higher than the level that was observed during the convalescent phase in the HFRS patients (Figure 1C, P<0.001). The sCD163 concentration was also obviously higher during the acute and convalescent phases in the HFRS patients compared with those in the normal controls (P<0.0001), (Figure 1C and 1D). The sCD163 plasma levels in the severe/critical group were higher than those in the mild/moderate group during the acute (P<0.0001) (Figure 1E). The plasma sCD163 levels in the mild/moderate group were compared with those in the severe/critical group, and only 4 (13.7%) of the 29 mild/moderate group cases had plasma sCD163 levels that were over 4 mg/l, while 28 (60.8%) of the 46 severe/critical group cases had sCD163 levels that were over 4 mg/l (a 4.3-fold change between the high vs. mild/moderate groups). These results demonstrate that there was some kind of an association between the plasma sCD163 concentrations and the disease severity during the HFRS course.

Bottom Line: The sCD163 plasma levels were measured using a sandwich ELISA, and the relationship between sCD163 and disease severity was analyzed.The results demonstrated that sCD163 plasma levels during the HFRS acute phase were significantly higher in patients than during the convalescent stage and the levels in the healthy controls (P<0.0001).The sCD163 plasma levels in the severe/critical group were higher than those in the mild/moderate group during the acute (P<0.0001).

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.

ABSTRACT

Background: Hantaan virus is a major zoonotic pathogen that causesing hemorrhagic fever with renal syndrome (HFRS). Although HFRS pathogenesis has not been entirely elucidated, the importance of host-related immune responses in HFRS pathogenesis has been widely recognized. CD163, a monocyte and macrophage-specific scavenger receptor that plays a vital function in the hosts can reduce inflammation, is shed during activation as soluble CD163 (sCD163). The aim of this study was to investigate the pathological significance of sCD163 in patients with HFRS.

Methods: Blood samples were collected from 81 hospitalized patients in Tangdu Hospital from October 2011 to January 2014 and from 15 healthy controls. The sCD163 plasma levels were measured using a sandwich ELISA, and the relationship between sCD163 and disease severity was analyzed. Furthermore, CD163 expression in 3 monocytes subset was analyzed by flow cytometry.

Results: The results demonstrated that sCD163 plasma levels during the HFRS acute phase were significantly higher in patients than during the convalescent stage and the levels in the healthy controls (P<0.0001). The sCD163 plasma levels in the severe/critical group were higher than those in the mild/moderate group during the acute (P<0.0001). A Spearman correlation analysis indicated that the sCD163 levels were positively correlated with white blood cell, serum creatine, blood urea nitrogen levels, while they were negatively correlated with blood platelet levels in the HFRS patients. The monocyte subsets were significantly altered during the acute stage. Though the CD163 expression levels within the monocyte subsets were increased during the acute stage, the highest CD163 expression level was observed in the CD14++CD16+ monocytes when compared with the other monocyte subsets.

Conclusion: sCD163 may be correlated with disease severity and the disease progression in HFRS patients; however, the underlying mechanisms should be explored further.

Show MeSH
Related in: MedlinePlus