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  • Consistent with prior reports this study

    2020-03-24

    Consistent with prior reports, this study also found the level of 11 cytokines (MIF, IL-1Ra, CTACK, M-CSF, Basic FGF, VCAM-1, SDF-1α, IL-8, IL-16, PDGF-β, and GRO-α) significantly decreased in the sera of adult HFMD patients in comparison with controls. MIF is a pro-inflammaory cytokine that is associated with disease severity and poor prognosis (de Jong et al., 2001, Roger et al., 2001). The decreased level of MIF in our study was in accordance with the fact that the adult cases of HFMD are generally mild and self-limited. IL-1Ra modulates a variety of IL-1 related inflammatory responses and is reported to be significantly elevated in HFMD patients (Wang et al., 2010, Di Mitri et al., 2014). CTACK is a skin-associated cytokine that plays a role in T cell mediated inflammation of the skin (Sigmundsdottir et al., 2007). On the contrary, we found the level of both IL-1Ra and CTACK are actually decreased in this study, which needs further explanation. Basic FGF promotes the wound healing of normal tissues (Barrientos et al., 2014). This study showed that the Methscopolamine mg of Basic FGF significantly decreased, which might be related with the oral ulcer and rash in adult patients with HFMD. Cytokines are involved in a variety of biological activities, and are important in host health and disease (Strowig et al., 2012, Rathinam and Fitzgerald, 2016, Lamkanfi and Dixit, 2014, Ogura et al., 2006). This study examined the correlation between cytokine expression and the clinical characteristics of adult patients with HFMD. Results showed a group of cytokines have positive correlation with clinical characteristics, whereas some cytokines are negatively correlated with clinical characteristics. Of note, clinical features ALT and GLU had a different correlation pattern. CA16 and EV71 are the predominate causative agents of HFMD, followed by CA6 and CA10 (Ministry of Health of the People’s Republic of China, 2018, Chang et al., 1999, Wang et al., 2015). The clinical features, therapy, and outcomes are various between the enteroviral genotypes, among which, EV71 infection may cause severe CNS complications and even fatal outcomes (Puenpa et al., 2018, Chang et al., 1999, Wang et al., 2015), while the CA6-associated HFMD presents atypical clinical features. The major change in clinical features of CA6-associated cases is skin rashes beyond the typical sites (hand, foot and mouth) for HFMD, including face, neck, and trunk (Bian et al., 2015). Clinicians may confuse the symptoms of CA6-associated HFMD with other exanthema illness. Thus, this study tried to identify the differential cytokine expression levels between the enteroviral genotypes. We found there is no difference in the expression level for most of the cytokines between enteroviral genotypes. All the genotypes presented cytokine dysregulation. The study identified five cytokines (TNF-α, IL-5, IL-8, IL-18, and CTACK) that were significantly different between enteroviral genotypes. This might indicate that various enteroviruses could cause different immune responses in the host upon infection. Having a better understanding of the inflammatory profiles is important for controlling the HFMD epidemic. There are no specific anti-viral therapy or multi-valent vaccines for HFMD (Takahashi et al., 2016, Zhu et al., 2014). Effectively identifying the HFMC cases and controlling the infection source are key to the prevention of HFMD outbreak. Few HFMD-specific markers are applicable in lab testing. Our study showed that the level of a group of cytokines is significantly different between adult patients of HFMD and the controls. Moreover, the expression of these cytokines was correlated with the clinical characteristics, and some of them were different between enteroviral genotypes. Thus, we tried to identify the adult cases of HFMD from the healthy controls with the cytokine expression profiles using Random forest method (Takahashi et al., 2016, Zhu et al., 2014). The results of the Random forest method showed that we can effectively classify the cytokine expression profiles into HFMD class and control class, with a very high prediction accuracy (AUC=0.91). These results revealed that inflammatory profiles have the potential to effectively identify the enteroviral infection.