Abstract
Enterovirus 71 (EV71) infection can develop devastating clinical outcomes such as brain stem encephalitis (BE) and pulmonary edema (PE). Alteration of human leukocyte antigen-G (HLA-G) expression or cytokine production was considered playing important roles in virus-related pathogenesis. However, clinical relevance of HLA-G in EV71 infection remains unknown. In the current study, patients were stratified by disease severity as BE (n = 107) and PE (n = 18). HLA-G expression on peripheral blood monocytes from patients with BE (n = 15), patients with PE (n = 15) and control subjects (n = 31) was analyzed with flow cytometry. Plasma soluble HLA-G (sHLA-G) (in 67 BE, 18 PE and 120 control subjects), IL-6 and IL-10 (in 50 patients with BE, 18 patients with PE and 45 control subjects) were determined with enzyme-linked immunosorbent assay. Data showed that the percentage of HLA-G-positive monocytes (mean 7.76 vs 3.68 %, p < 0.001), levels for sHLA-G (median 129.2 vs 70.6 U/ml, p < 0.001), IL-10 (median 160.5 vs 29.5 pg/ml, p < 0.001) and IL-6 (median 20.50 vs 5.21 pg/ml, p = 0.002) was significantly higher in patients with PE than in patients with BE. Taken together, our findings indicated that elevation of HLA-G expression on monocytes, plasma sHLA-G, IL-10 and IL-6 levels was associated with PE in patients infected with EV71.
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References
Schmidt NJ, Lennette EH, Ho HH (1974) An apparently new enterovirus isolated from patients with disease of the central nervous system. J Infect Dis 129:304–309
Solomon T, Lewthwaite P, Perera D, Cardosa MJ, McMinn P, Ooi MH (2010) Virology, epidemiology, pathogenesis, and control of enterovirus 71. Lancet Infect Dis 10:778–790
Lee TC, Guo HR, Su HJ, Yang YC, Chang HL, Chen KT (2009) Diseases caused by enterovirus 71 infection. Pediatr Infect Dis J 28:904–910
Alzhanova D, Früh K (2010) Modulation of the host immune response by cowpox virus. Microbes Infect 12:900–909
Lin A, Xu H, Yan W (2007) Modulation of HLA expression in human cytomegalovirus immune evasion. Cell Mol Immunol 4:91–98
Hansen TH, Bouvier M (2009) MHC class I antigen presentation: learning from viral evasion strategies. Nat Rev Immunol 9:503–513
Lin TY, Chang LY, Huang YC, Hsu KH, Chiu CH, Yang KD (2002) Different proinflammatory reactions in fatal and non-fatal enterovirus 71 infections: implications for early recognition and therapy. Acta Paediatr 91:632–635
Wang SM, Lei HY, Yu CK, Wang JR, Su IJ, Liu CC (2008) Acute chemokine response in the blood and cerebrospinal fluid of children with enterovirus 71-associated brainstem encephalitis. J Infect Dis 198:1002–1006
Wang SM, Lei HY, Su LY, Wu JM, Yu CK, Wang JR, Liu CC (2007) Cerebrospinal fluid cytokines in enterovirus 71 brain stem encephalitis and echovirus meningitis infections of varying severity. Clin Microbiol Infect 13:677–682
Wang SM, Lei HY, Huang KJ, Wu JM, Wang JR, Yu CK, Su IJ, Liu CC (2003) Pathogenesis of enterovirus 71 brainstem encephalitis in pediatric patients: roles of cytokines and cellular immune activation in patients with pulmonary edema. J Infect Dis 188:564–570
Lafon M (2008) Immune evasion, a critical strategy for rabies virus. Dev Biol (Basel) 131:413–419
Carosella ED, HoWangYin KY, Favier B, LeMaoult J (2008) HLA-G-dependent suppressor cells: diverse by nature, function, and significance. Hum Immunol 69:700–707
Paul P, Cabestre FA, Ibrahim EC, Lefebvre S, Khalil-Daher I, Vazeux G, Quiles RM, Bermond F, Dausset J, Carosella ED (2000) Identification of HLA-G7 as a new splice variant of the HLA-G mRNA and expression of soluble HLA-G5, -G6, and -G7 transcripts in human transfected cells. Hum Immunol 61:1138–1149
Carosella ED, Moreau P, Lemaoult J, Rouas-Freiss N (2008) HLA-G: from biology to clinical benefits. Trends Immunol 29:125–132
Wang SM, Liu CC (2009) Enterovirus 71: epidemiology, pathogenesis and management. Expert Rev Anti Infect Ther 7:735–742
Sun LM, Zheng HY, Zheng HZ, Guo X, He JF, Guan DW, Kang M, Liu Z, Ke CW, Li JS, Liu L, Guo RN, Yoshida H, Lin JY (2011) An enterovirus 71 epidemic in Guangdong Province of China, 2008: epidemiological, clinical, and virogenic manifestations. Jpn J Infect Dis 64:13–18
Hunt JS, Langat DL (2009) HLA-G: a human pregnancy-related immunomodulator. Curr Opin Pharmacol 9:462–469
Rizzo R, Vercammen M, van de Velde H, Horn PA, Rebmann V (2011) The importance of HLA-G expression in embryos, trophoblast cells, and embryonic stem cells. Cell Mol Life Sci 68:341–352
Deschaseaux F, Delgado D, Pistoia V, Giuliani M, Morandi F, Durrbach A (2011) HLA-G in organ transplantation: towards clinical applications. Cell Mol Life Sci 68:397–404
Yan WH (2011) HLA-G expression in cancers: potential role in diagnosis, prognosis and therapy. Endocr Metab Immune Disord Drug Targets 11:76–89
Gregori S, Magnani CF, Roncarolo MG (2009) Role of human leukocyte antigen-G in the induction of adaptive type 1 regulatory T cells. Hum Immunol 70:966–969
Trinh QD, Izumi Y, Komine-Aizawa S, Shibata T, Shimotai Y, Kuroda K, Mizuguchi M, Ushijima H, Mor G, Hayakawa S (2009) H3N2 influenza A virus replicates in immortalized human first trimester trophoblast cell lines and induces their rapid apoptosis. Am J Reprod Immunol 62:139–146
Chen HX, Chen BG, Shi WW, Zhen R, Xu DP, Lin A, Yan WH (2011) Induction of cell surface human leukocyte antigen-G expression in pandemic H1N1 2009 and seasonal H1N1 influenza virus-infected patients. Hum Immunol 72:159–165
Yan WH, Lin A, Chen BG, Chen SY (2009) Induction of both membrane-bound and soluble HLA-G expression in active human cytomegalovirus infection. J Infect Dis 200:820–826
Onno M, Pangault C, Le Friec G, Guilloux V, André P, Fauchet R (2000) Modulation of HLA-G antigens expression by human cytomegalovirus: specific induction in activated macrophages harboring human cytomegalovirus infection. J Immunol 164:6426–6434
Lajoie J, Fontaine J, Tremblay C, Routy JP, Poudrier J, Roger M (2009) Persistence of high levels of blood soluble human leukocyte antigen-G is associated with rapid progression of HIV infection. AIDS 23:1437–1440
Lozano JM, González R, Kindelán JM, Rouas-Freiss N, Caballos R, Dausset J, Carosella ED, Peña J (2002) Monocytes and T lymphocytes in HIV-1-positive patients express HLA-G molecule. AIDS 16:347–351
Weng PJ, Fu YM, Ding SX, Xu DP, Lin A, Yan WH (2011) Elevation of plasma soluble human leukocyte antigen-G in patients with chronic hepatitis C virus infection. Hum Immunol 72:406–411
Souto FJ, Crispim JC, Ferreira SC, da Silva AS, Bassi CL, Soares CP, Zucoloto S, Rouas-Freiss N, Moreau P, Martinelli AL, Donadi EA (2011) Liver HLA-G expression is associated with multiple clinical and histopathological forms of chronic hepatitis B virus infection. J Viral Hepat 18:102–105
Lafon M, Prehaud C, Megret F, Lafage M, Mouillot G, Roa M, Moreau P, Rouas-Freiss N, Carosella ED (2005) Modulation of HLA-G expression in human neural cells after neurotropic viral infections. J Virol 79:15226–15237
Mégret F, Prehaud C, Lafage M, Moreau P, Rouas-Freiss N, Carosella ED, Lafon M (2007) Modulation of HLA-G and HLA-E expression in human neuronal cells after rabies virus or herpes virus simplex type 1 infections. Hum Immunol 68:294–302
Shi WW, Lin A, Xu DP, Bao WG, Zhang JG, Chen SY, Li J, Yan WH (2011) Plasma soluble human leukocyte antigen-G expression is a potential clinical biomarker in patients with hepatitis B virus infection. Hum Immunol 72:1068–1073
Wang SM, Ho TS, Shen CF, Liu CC (2008) Enterovirus 71, one virus and many stories. Pediatr Neonatol 49:113–115
Lin TY, Hsia SH, Huang YC, Wu CT, Chang LY (2003) Proinflammatory cytokine reactions in enterovirus 71 infections of the central nervous system. Clin Infect Dis 36:269–274
Weng KF, Chen LL, Huang PN, Shih SR (2010) Neural pathogenesis of enterovirus 71 infection. Microbes Infect 12:505–510
Khong WX, Foo DG, Trasti SL, Tan EL, Alonso S (2011) Sustained high levels of interleukin-6 contribute to the pathogenesis of enterovirus 71 in a neonate mouse model. J Virol 85:3067–3076
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This work was supported by Zhejiang Provincial program for the cultivation of high-level innovative health talents and by the grants from National Science Foundation of China (No. 81071365), Science and Technology Bureau of Zhejiang Province (Nos. 2010KYA137, 2009C33147) and Key science and Technology innovation Team of Zhejiang Province (2012R10048-11).
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Zheng, XQ., Chen, XQ., Gao, Y. et al. Elevation of human leukocyte antigen-G expression is associated with the severe encephalitis associated with neurogenic pulmonary edema caused by Enterovirus 71. Clin Exp Med 14, 161–167 (2014). https://doi.org/10.1007/s10238-013-0237-6
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DOI: https://doi.org/10.1007/s10238-013-0237-6