Induction of Both Membrane‐Bound and Soluble HLA‐G Expression in Active Human Cytomegalovirus Infection

Abstract

Alteration of HLA expression or cytokine production plays a crucial role in the pathogenesis of human cytomegalovirus (HCMV) infection. HLA-G has been suggested to be involved in HCMV infection, and modulation of HLA-G expression by interferon (IFN)-gamma and interleukin (IL)-10 has been reported. However, the clinical relevance of HLA-G in HCMV infection remains unknown. The study included 75 patients with active HCMV infection (age range, 1-4.5 years) and 150 sex- and age-matched healthy control subjects (age range, 1-5 years). HLA-G expression in peripheral monocytes from patients (n=38) and control subjects (n=20) was analyzed using flow cytometry. Plasma levels of soluble HLA-G (in 75 patients and 150 control subjects), IL-10 (in 75 patients and 40 control subjects), and IFN-gamma (in 75 patients and 40 control subjects) were determined using enzyme-linked immunosorbent assay. The mean percentage of HLA-G-positive monocytes among patients with active HCMV infection was dramatically increased, compared with that among healthy control subjects (6.33% vs 1.64%; P<.001). Similarly, significant increases were observed in soluble HLA-G level (median, 54.91 vs 21.32 U/mL; P<.001) and IL-10 level (median, 9.24 vs 1.82 ng/mL; P<.001). Although the expression of IFN-gamma was higher in patients with active HCMV infection than in healthy control subjects, the difference was not statistically significant (median, 1254.46 vs 887.05 ng/mL; P=.070). Furthermore, no correlation was established between HLA-G expression and levels of IL-10 or IFN-gamma. HLA-G expression in monocytes and plasma soluble HLA-G and IL-10 levels were increased during active HCMV infection.