Elevated Soluble HLA-G Levels Associate With Dengue Severity in Vietnamese Patients

Abstract

The pathogenesis of dengue remains complex and incompletely understood. One proposed mechanism involves the virus evading host immune responses through the upregulation and/or secretion of immune-inhibitory molecules. This study investigates the association between plasma levels of soluble human leukocyte antigen G (sHLA-G), a known immunoregulatory molecule, and dengue severity in hospitalized patients. A total of 238 dengue patients and 118 healthy controls were enrolled. Dengue infection was confirmed by real-time RT-PCR, and patients were clinically categorized as having dengue fever without warning signs (DF), dengue with warning signs (DWS), or severe dengue (SD), according to WHO guidelines. Laboratory parameters were assessed upon hospital admission, and plasma sHLA-G levels were measured using ELISA. sHLA-G levels were significantly elevated in dengue patients compared to healthy controls (median [range]: 42.7 [7.10-1300] U/mL vs. 11.1 [4.7-620] U/mL; p < 0.001). After adjusting for age, sex and disease severity, a significant association was observed between sHLA-G levels and days of illness (β = 0.1, p = 0.03). Patients requiring close medical monitoring (DWS/SD) showed higher sHLA-G levels (51.0 [7.17-525] U/mL) than those having dengue fever without warning signs (38.0 [7.10-1300] U/mL); p = 0.011. While ALT and AST were positively correlated with sHLA-G levels in all patients, total lymphocyte counts were inversely correlated with sHLA-G in severe cases (r = -0.78, p = 0.002). Elevated sHLA-G levels are associated with dengue severity and may serve as a useful marker for identifying high-risk cases and for guiding clinical monitoring. Clinical trial registration: Not applicable.

Keywords: Vietnam; clinical severity; dengue; sHLA‐G.

Figure 1

sHLA‐G plasma levels in dengue patients and its clinical relevance. (a) sHLA‐G plasma levels in dengue patients and healthy controls. (b) sHLA‐G plasma levels in dengue patients of varying severity. (c) sHLA‐G plasma levels in dengue patients by medical monitoring requirements. sHLA‐G plasma levels were determined using a commercially available ELISA as described in Methods. The data are provided as box plots as log‐transformed sHLA‐G (U/mL).

Figure 2

sHLA‐G levels and day of illness multiple linear regression was performed adjusting disease severity to estimate the association between log‐transformed sHLA‐G levels and days of illness.