Table 1.
Immunological parameters as potential biomarkers
| Immune marker | Disease phase | Comment |
|---|---|---|
| Elevated levels | ||
| IL-4, IL-6, IL-8, IL-10 | Elevated during the febrile phase, peaking around defervescence | Elevated levels in patients with DSS compared with those with DF, which correlated with markers of disease severity [58]. IL-10 correlated with degree of thrombocytopenia [49,65] |
| TNFa, sTNFR-75, sTNFR-80 | Elevated in the febrile phase | Raised levels in severe dengue versus mild disease. Positive correlation with disease severity. sTNFRspredicted children who subsequently went on to develop shock [64,67] |
| IFN-γ | Raised in early febrile phase, peaking prior to defervescence day | DHF was associated with earlier peak IFN-γ levels [49]. Associated with development of severe disease [59] |
| MIP-1b, G-CSF, IP-10, MCP-1 | Elevated in early febrile phase through to defervescence | Compared with healthy control, MIP-1b and G-CSF were elevated in patients with uncomplicated dengue; MCP-1 in dengue with warning signs; and IP-10 in both groups [62] |
| C3a, C4a, C5a,Factor D | Elevated in acute phase | Elevated in DHF compared with DF [68] |
| SC5b-9 terminal complement complex | Elevated in acute disease ,peaking day after defervescence | Higher levels were demonstrated in DF/DHF compared with OFI, and correlated with dengue severity [54] |
| Reduced levels | ||
| RANTES/CCL5 | Reduced levels during the acute phase | Reduced during acute phase in patients with dengue compared with healthy controls, and correlated with thrombocytopenia [66] |
| IL1-b, IL-2, EGF | Reduced levels during febrile phase | No difference was demonstrated between the severity grades for IL-1b but there was significantly lower levels of IL-2 and EGF in DSS compared with DF [58] |
| VEGF, VEGFR2 | Altered levels of VEGF and VEGFR2 around day of defervescence | There are mixed reports of VEGF levels |
| One study demonstrated reduced VEGF levels in DSS compared with DF from 2 days before to 2 days after defervescence [58]. Other studies have shown elevated VEGF levels in DHF compared with DF[69], and a further study demonstrated elevated levels of free VEGF in DHF at the time of plasma leakage, and reduced levels of VEGFR2 [63] | ||
| C3, factor H | Reduced levels during acute dengue | Reduced levels were found in patients with DHF compared with those with DF and healthy controls [68] |
C, complement; DF, dengue fever; DHF, dengue haemorrhagic fever; DSS, dengue shock syndrome;EGF, epidermal growth factor; G-CSF, granulocyte-colony stimulating factor; IFN, interferon; IL, interleukin; IP, interferon-γ-induced protein; MCP, monocyte chemoattractant protein; MIP, macrophage inflammatory protein; OFI, other febrile illness; RANTES/CCL5, regulated on activation, normal T cell expressed and secreted/chemokine (C-C motif) ligand 5; TNF, tumour necrosis factor; sTNFR, soluble tumour necrosis factor receptor; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor.