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  • This study had some limitations First a


    This study had some limitations. First, a small number of HP patients were enrolled because of the extreme rarity of this disease, which may have caused some selection bias. Yokoseki et al., found no increase in Th2 cytokines, such as IL-4, in IHP patients (Yokoseki et al., 2014). The sensitivity of different detection methods used between these two studies might have led to the different results observed. Given that our study and that of Yokoseki et al. (2014) used limited numbers of IHP patients, the heterogeneity of IHP as shown in this study and selection bias might also account for this discrepancy. To solve this issue, larger samples of IHP cases are needed for future studies. Second, we did not study serum cytokine/chemokine levels in the present study. We think CSF cytokine/chemokine levels might reflect dural urat1 inhibitor more than serum levels because IHP is usually a localized disease of the dura mater rather than a systemic disease. Although these limitations should be taken in mind, we found significant changes in CSF Th2 cytokine/chemokine levels in our IHP patients. Although these findings should be regarded as preliminary, we think Th2 cell involvement in HP pathogenesis is worth investigating. The following are the supplementary data related to this article.
    Introduction Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease that has overwhelmed the Asia-Pacific region in recent years (Xing et al., 2014, Puenpa et al., 2018, Anh et al., 2018, Fujimoto et al., 2012). The incidence rate (IR) of HFMD is between 37.01/100,000 to 205.06/100,000 in China, with a case-fatality rate of 6.46/100,000 to 51.00/100,000 (Ministry of Health of the People’s Republic of China, 2018). Patients typically present with fever, oral ulcer, and rash on hand, foot, and buttock (Chang et al., 1999, Wang et al., 2015). Enterovirus 71 (EV71) and Coxsackie virus A16 (CA16) are the major causative agents of HFMD, followed by Coxsackie virus A6 (CA6) and Coxsackie virus A10 (CA10) (Pérez-Vélez et al., 2007, WHO, 2011). The enterovirus infection always accompanies acute inflammatory response. Inflammation is characterized by the accumulation of inflammatory mediators such as cytokines (Hotamisligil, 2017, Strowig et al., 2012). Cytokines are a group of small secretory proteins mediating diverse immunomodulation (Rathinam and Fitzgerald, 2016, Lamkanfi and Dixit, 2014, Ogura et al., 2006). Numerous reports showed that cytokines are important in the occurrence, development, and prevalence of infectious disease (Paul and Seder, 1994, Fauci, 1996, Premack and Schall, 1996, Yazdanbakhsh et al., 2002, Baxt et al., 2013, Horner and Gale, 2013). Previous studies proved that HFMD pathogenesis and progression are related with elevated level of cytokines (Lin et al., 2002, Zeng et al., 2013, Ye et al., 2015). However, there is no study that examined the cytokine expression profiles in adult patients of HFMD. Child patients and subclinical carriers are the main source of enteroviral infection (Ministry of Health of the People’s Republic of China, 2018). Although HFMD is uncommon among adults, our previous study showed that adults might act as potential enterovirus reservoirs (Yin et al., 2014). In addition, the increasing social activities and travels of adults may cause the trans-regional spread of HFMD (Fang et al., 2018). Moreover, CA6, the recent prevalent genotype, is reported as having high morbidity in adults (Bian et al., 2015). Thus, identifying the association between the dysregulation of cytokines and the development and prognosis of HFMD in adult patients has vital clinical significance. This study systematically analyzed serum levels of inflammatory cytokines in adult patients with HFMD and associated them with the clinical characteristics and enterovirus genotypes. We also tried to identify the adult cases of HFMD from the healthy controls using the inflammatory profiles with machine learning algorithm.