Value of abnormal HLA-DR expression on CD14+ monocytes in estimating immune function status and clinical prognosis of patients with hand, foot and mouth disease / 中华微生物学和免疫学杂志

ABSTRACT

Objective To investigate the value of abnormal expression of HLA-DR on peripheral blood monocytes in evaluating the immune function status, clinical prognosis and severity of patients with hand, foot and mouth disease (HFMD). Methods From June 2017 to October 2018, 100 cases of mild HFMD, 80 cases of severe HFMD, 32 cases of critical HFMD and 40 healthy children (control group) were recruited in this study. The patients were divided into two groups, lower DR group (DR-L, HLA-DR expres-sion<30％ ) and normal DR group (DR-N,HLA-DR expression>30％ ) according to the HLA-DR expression on monocytes. Flow cytometry was used to detect the CD14+ monocytes expressing HLA-DR and the absolute count of lymphocyte subsets. Immunoturbidimetry was used to detect the levels of IgG, IgM and IgA in plas-ma samples. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of IFN-γ and IL-10 in plasma samples. Pediatric critical illness score ( PCIS) and the pediatric risk of mortality Ⅲ(PRISM Ⅲ) were used to estimate the severity of HFMD. Results ① There were significant differences in HLA-DR expression on monocytes among children with mild, severe and critical HFMD (F = 47. 102, P<0. 05). Patients with critical HFMD had the lowest HLA-DR expression (P<0. 05). ② The numbers of CD14+ monocytes, CD3+T cells, CD4+T cells, CD8+T cells, B cells and NK cells in peripheral blood of the DR-L group were significantly lower than those of the DR-N group and the normal group, especially in pa-tients with severe or critical HFMD (P<0. 05). ③ There was no significant difference in the level of IgG, IgA or IgM among the DR-L, DR-N and control groups (P>0. 05). ④ Compared with the DR-N group, the DR-L group showed decreased IFN-γ level and increased IL-10 level in plasma (P<0. 05). The ratio of IFN-γ/ IL-10 of the DR-L group was lower than that of the DR-N group and control group (P<0. 05). HLA-DR expression was negatively correlated with the concentration of IL-10 in plasma (r= -0. 704, P<0. 05), and positively correlated with the IFN-γ/ IL-10 ratio (r = 0. 773, P<0. 05). ⑤ Compared with the DR-N group, the DR-L group showed lower PCIS and higher PRISM Ⅲ. HLA-DR expression was positively corre-lated with PCIS (r=0. 715, P=0. 00) and negatively correlated with PRISM Ⅲ (r = -0. 610, P = 0. 00).⑥ The incidence of pulmonary edema, pulmonary hemorrhage and cardiopulmonary failure and the mortality of HFMD patients in the DR-L group were significantly higher than those in the DR-N group (P<0. 05).Conclusions Patients with severe or critical HFMD had cellular immune dysfunction and abnormal HLA-DR expression on CD14+ monocytes. Assessing the expression of HLA-DR on monocytes could be used to evaluate the cellular immunity of patients with severe or critical HFMD. Lower expression of HLA-DR on CD14+ monocytes might be associated with severe HFMD and poor prognosis.