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Increased Serum Hyaluronic Acid and Heparan Sulfate in Dengue Fever: Association with Plasma Leakage and Disease Severity

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ABSTRACT

Plasma leakage is a major pathogenic mechanism of severe dengue, but the etiology remains unclear. The association between endothelial glycocalyx integrity and vascular permeability in older adults with dengue has not been evaluated. A prospective cohort study of adults with undifferentiated fever screened for dengue by RT-PCR or NS1 antigen testing was performed. Patients were assessed daily while symptomatic and at convalescence. Serum hyaluronic acid (HA), heparan sulfate (HS) and selected cytokines (TNF-α, IL-6, IL-10) were measured on enrollment and convalescence. Patients were diagnosed as dengue fever (DF, n = 30), dengue hemorrhagic fever (DHF, n = 20) and non-dengue (ND) febrile illness (n = 11). Acute HA and HS levels were significantly higher in all dengue patients compared to ND (p = 0.0033 and p = 0.0441 respectively), but not different between DF and DHF (p = 0.3426 and p = 0.9180 respectively). Enrolment HA inversely correlated with serum albumin, protein and platelets in all dengue and DHF (p < 0.05). HA and HS in all dengue patients decreased significantly at convalescence. Serum IL-10 was significantly associated with HA in all dengue patients (p = 0.002). Serum HA and HS levels were increased in adult dengue and HA was associated with markers of disease severity. Endothelial glycocalyx damage may have a role in vascular leakage in dengue.

No MeSH data available.


Longitudinal trend of serum hyaluronic acid (HA) and heparan sulfate (HS) level: (a) Serum HA in DF group, (b) Serum HA in DHF group, (c) Serum HS in DF group (1 patient was excluded for outlying values), (d) Serum HS in DHF group.
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f2: Longitudinal trend of serum hyaluronic acid (HA) and heparan sulfate (HS) level: (a) Serum HA in DF group, (b) Serum HA in DHF group, (c) Serum HS in DF group (1 patient was excluded for outlying values), (d) Serum HS in DHF group.

Mentions: Summary statistics of serum HA and HS are summarized in Table 2. On enrollment, HA levels were significantly higher in all dengue patients (DHF plus DF) compared to non-dengue febrile patients (p = 0.0033) (Fig. 1a). In dengue patients, acute HA levels in DHF patients were not significantly higher than the DF patients (p = 0.3426, Fig. 1b). When analyzed by day of illness, there were also no significant differences between DF and DHF patients enrolled on the third, fourth or fifth day of illness (first day of illness is defined as the day of fever onset). Acute serum HA was significantly higher in patients with secondary DENV infection when compared to those with primary infection (p = 0.0088, Fig. 1c). Patients enrolled on the fifth day of illness had significantly higher HA levels of HA compared to those enrolled on the fourth day, who correspondingly had higher concentrations than those enrolled on the third day, (Fig. 1d). With clinical recovery after discharge, there was a significant decrease in acute serum HA levels compared to convalescent serum HA levels in both DF and DHF groups (p < 0.001, Fig. 2a and b) but not in the non-dengue group (p = 0.6448).


Increased Serum Hyaluronic Acid and Heparan Sulfate in Dengue Fever: Association with Plasma Leakage and Disease Severity
Longitudinal trend of serum hyaluronic acid (HA) and heparan sulfate (HS) level: (a) Serum HA in DF group, (b) Serum HA in DHF group, (c) Serum HS in DF group (1 patient was excluded for outlying values), (d) Serum HS in DHF group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5385535&req=5

f2: Longitudinal trend of serum hyaluronic acid (HA) and heparan sulfate (HS) level: (a) Serum HA in DF group, (b) Serum HA in DHF group, (c) Serum HS in DF group (1 patient was excluded for outlying values), (d) Serum HS in DHF group.
Mentions: Summary statistics of serum HA and HS are summarized in Table 2. On enrollment, HA levels were significantly higher in all dengue patients (DHF plus DF) compared to non-dengue febrile patients (p = 0.0033) (Fig. 1a). In dengue patients, acute HA levels in DHF patients were not significantly higher than the DF patients (p = 0.3426, Fig. 1b). When analyzed by day of illness, there were also no significant differences between DF and DHF patients enrolled on the third, fourth or fifth day of illness (first day of illness is defined as the day of fever onset). Acute serum HA was significantly higher in patients with secondary DENV infection when compared to those with primary infection (p = 0.0088, Fig. 1c). Patients enrolled on the fifth day of illness had significantly higher HA levels of HA compared to those enrolled on the fourth day, who correspondingly had higher concentrations than those enrolled on the third day, (Fig. 1d). With clinical recovery after discharge, there was a significant decrease in acute serum HA levels compared to convalescent serum HA levels in both DF and DHF groups (p < 0.001, Fig. 2a and b) but not in the non-dengue group (p = 0.6448).

View Article: PubMed Central - PubMed

ABSTRACT

Plasma leakage is a major pathogenic mechanism of severe dengue, but the etiology remains unclear. The association between endothelial glycocalyx integrity and vascular permeability in older adults with dengue has not been evaluated. A prospective cohort study of adults with undifferentiated fever screened for dengue by RT-PCR or NS1 antigen testing was performed. Patients were assessed daily while symptomatic and at convalescence. Serum hyaluronic acid (HA), heparan sulfate (HS) and selected cytokines (TNF-&alpha;, IL-6, IL-10) were measured on enrollment and convalescence. Patients were diagnosed as dengue fever (DF, n&thinsp;=&thinsp;30), dengue hemorrhagic fever (DHF, n&thinsp;=&thinsp;20) and non-dengue (ND) febrile illness (n&thinsp;=&thinsp;11). Acute HA and HS levels were significantly higher in all dengue patients compared to ND (p&thinsp;=&thinsp;0.0033 and p&thinsp;=&thinsp;0.0441 respectively), but not different between DF and DHF (p&thinsp;=&thinsp;0.3426 and p&thinsp;=&thinsp;0.9180 respectively). Enrolment HA inversely correlated with serum albumin, protein and platelets in all dengue and DHF (p&thinsp;&lt;&thinsp;0.05). HA and HS in all dengue patients decreased significantly at convalescence. Serum IL-10 was significantly associated with HA in all dengue patients (p&thinsp;=&thinsp;0.002). Serum HA and HS levels were increased in adult dengue and HA was associated with markers of disease severity. Endothelial glycocalyx damage may have a role in vascular leakage in dengue.

No MeSH data available.