Abstract:

Objective To investigate the differential diagnosis value for viral encephalitis（VE） and autoimmune encephalitis（AE） in children，by determining 12 cytokines，including interleukin （IL）-1β，IL-2，IL-4，IL-5，IL-6，IL-8，IL-10，IL-12P70，IL-17，interferon-gamma（INF- γ），interferon-alpha（INF- α）and tumor necrosis factor-alpha（TNF- α）in peripheral blood，and lymphocyte subsets natural killer（CD3+T cell，CD3+CD4⁺T cell，CD3+CD8⁺T cell，CD3-CD19+B cell and CD3-CD16+CD56+ natural killer cell） in peripheral blood. Methods Totally，60 pediatric patients with AE（AE group），40 pediatric patients with VE（VE group） and 60 healthy children（control group） were enrolled from May 2020 to May 2024. Using flow cytometry，lymphocyte subsets and 12 cytokines in peripheral blood were determined. Receiver operating characteristic（ROC）was used to estimate the efficiency of differential diagnosis between AE and VE with these various indicators. Results The absolute value of CD3-CD19+B cells in VE group was higher than that in healthy control group（P<0.10），and the absolute value of CD3-CD16+CD56+ natural killer cell cells in VE group was lower than that in healthy control group（P<0.10）. The absolute value of CD3-CD16+CD56+ natural killer cell cells in AE group was lower than that in healthy control group（P<0.10）. The absolute number of CD3+CD8⁺T cells in VE group was lower than that in AE group（P<0.10），and the absolute value of CD3-CD19+B cells was higher than that in AE groups（P<0.10）. Except IL-17，the levels of the other cytokines in VE group were significantly different from those in healthy control group（P<0.10）. There was statistical significance for IL-4，IL-6，IL-8，IL-10 and TNF-α between AE and healthy control group（P<0.10）. The levels of IL-4，IL-6，IL-8，IL-10 and TNF-α in AE group were significantly different from those in healthy control group （P<0.10）. The levels of IL-4，IL-8，IL-10 and INF-γ in VE group were significantly different from those in AE group（P<0.10）. In VE group，IL-8 was positively correlated with IL-10（r=0.588，P<0.05），and INF-γ was positively correlated with IL-4 and IL-8 （r values were 0.322 and 0.426，P<0.05）. In AE group，IL-4 was positively correlated with IL-10（r=0.833，P<0.05），IL-8 was positively correlated with IL-4 and IL-10（r values were 0.437 and 0.460，P<0.05），and TNF-α was positively correlated with IL-10（r=0.420，P<0.05）. There was no correlation between the absolute value of lymphocyte subsets and all cytokines in AE and VE groups（P>0.05）. The areas under curves（AUC）of CD3+CD8⁺T cell absolute value，B cell absolute value，IL-4，IL-8，IL-10 and INF-γ for differentiating AE and VE were 0.599，0.638，0.616，0.603，0.636 and 0.598，respectively. The AUC of the combined cytokine determination model and the combined lymphocyte subset and cytokine determination model were 0.687 and 0.756，respectively. Conclusions Peripheral blood lymphocyte subsets and cytokines may be used as auxiliary indicators in the differential diagnosis of VE and AE in children.

Key words: Lymphocyte subset, Cytokine, Autoimmune encephalitis, Viral encephalitis, Children