Immunology Letters 165 (2015) 60–61
Contents lists available at ScienceDirect
Immunology Letters journal homepage: www.elsevier.com/locate/immlet
Letter to the Editor
Hepatitis B virus (HBV) infection and multiple sclerosis: One more reason to undergo vaccination? Over the last two decades extensive research has asked whether there is any link between HB vaccination and the risk of developing MS [1–4]. Most of these publications reported the absence of a link or a slightly increased risk, but not sufficiently significant on the statistical level [2–4]. Recently, a study from France has highlighted a correlation between HB vaccination and MS with the application of Hill’s criteria to the data [4]. However, all this is expected to require further epidemiological studies, particularly from the French health insurance data [3,4]. Therefore, on the basis of the current data, there is no need to modify the vaccination recommendations [2–4]. MS is an inflammatory disease of the central nervous system (CNS) characterized by an autoimmune response against the myelin sheaths and axons, leading to progressive neurological dysfunction with a variable clinical course [5]. An increasing bulk of data suggest that osteopontin (OPN) may be involved in MS development and, especially, progression [5,6]. OPN is an integrin-binding glycoprotein also known as secreted phosphoprotein 1 (SPP1) functioning as a free cytokine in body fluids or as an immobilized extracellular matrix molecule in mineralized tissue [5–7]. OPN has been described to influence the development of several autoimmune diseases through the OPN immunoregulatory effects up-regulating the pro-inflammatory cytokines from both T helper type 1(TH1) and T helper type 17 (TH17) cell pathways [5,6]. It has been shown that OPN transcript is abundant in plaques dissected from brain of patients affected by MS, whereas it is absent in control brain tissue [5,6]. Concordantly, IL-17 secreting TH17 cells have been found to be elevated in MS patients [8]. HB virus infection is a worldwide public health problem of major concern [9,10]. It attacks the liver and can cause both acute and chronic disease including cirrhosis and hepatocellular carcinoma (HCC) with an incidence of 620.000 death per year [9–11]. It has been estimated that approximately 4.5 million new HBV infections occur worldwide each year, of which a quarter progress to liver disease and cirrhosis [10,11]. Vaccination with recombinant Hepatitis B virus surface antigen (HbsAg) is considered as the main valuable strategy for controlling and preventing HBV infection and its long-term serious sequelae, on global scale, both in terms of cost-effectiveness and benefit-cost ratios [10,12]. The implementation of large-scale programs of vaccination against HBV has led to a substantial decrease in disease burden, in the carrier rate and in HBrelated morbidity and mortality [9–11]. Thus, according to the WHO recommendations, universal vaccination has been currently implemented in 168 countries worldwide with an outstanding record of safety and efficacy [9–12]. HCC is one of the most frequent solid tumors occurring worldwide [12]. Chronic infection with HBV has
been connected epidemiologically with the development of HCC for more than 30 years [12]. Interestingly, an increased expression of OPN has been observed in HBV-related HCC [7,13]. The levels of OPN has been closely related to capsular infiltration, venous invasion, lymph node metastatis, and also with worse prognosis, implying that OPN may be a useful molecular marker for predicting the prognosis of HCC [7,13]. Moreover, it has been demonstrated that IL-17 expression is associated with the progression of HBV related chronic liver diseases, especially in the formation of liver fibrosis that is a major link in the development of cirrhosis [14]. With respect to the above, we advance the hypothesis that patients with MS may be at a higher risk of HB-related chronic liver disease, cirrhosis, and HCC as a consequence of the increased expression of both OPN and IL17. Therefore, HB vaccination is especially important for this category of patients. We speculate that HB vaccination should be strongly recommended for children and younger adults who have not been previously vaccinated against HB taking into account that HBV infection is highly contagious and there is no conclusive evidence that HBV vaccination is associated with the risk of MS.
References [1] Ascherio A, Zhang SM, Hernán MA, Olek MJ, Coplan PM, Brodovicz K, Walker AM. Hepatitis B vaccination and the risk of multiple sclerosis. N Engl J Med 2001;344(February (5)):327–32. [2] Hernán MA, Jick SS, Olek MJ, Jick H. Recombinant hepatitis B vaccine and the risk of multiple sclerosis: a prospective study. Neurology 2004;63(September (5)):838–42. [3] Martinez-Sernandez V, Figueiras A. Central nervous system demyelinating diseases and recombinant hepatitis B vaccination: a critical review of scientific production. J Neurol 2013;260:1951–9. [4] Le Houézec D. Evolution of multiple sclerosis in France since the beginning of hepatitis B vaccination. Immunol Res 2014;60(December (2–3)): 219–25. [5] Comi C, Cappellano G, Chiocchetti A, Orilieri E, et al. The impact of osteopontin gene variations on multiple sclerosis development and progression. Clin Dev Immunol 2012;2012:212893. [6] Shimizu Y, Ota K, Ikeguchi R, Kubo S, Kabasawa C, Uchiyama S. Plasma osteopontin levels are associated with disease activity in the patients with multiple sclerosis and neuromyelitis optica. J Neuroimmunol 2013;263(1–2): 148–51. [7] Liang KH, Yeh CT. OPN sesame. Hepatobiliary Surg Nutr 2014;3:112–4. [8] Babaloo Z, Aliparasti M, Babaie F, Almasi S, Baradaran B, Farhoodi M. The role of Th17 cells in patients with relapsing-remitting multiple sclerosis: interleukin17A and interleukin-17F serum levels. Immunol Lett 2015;164(2):76–80. [9] Romano L, Paladini S, Galli C, Raimonido G, Pollicino T, Zanetti AR. Hepatitis B vaccination. Hum Vaccin Immunother 2015;11:53–7. [10] Zanetti AR, Van Damme P, Shouval D. The global impact of vaccination against hepatitis B: a historical overview. Vaccine 2008;26(November (49)): 6266–73. [11] Goldstein ST, Zhou F, Hadler SC, Bell BP, Mast EE, Margolis HS. A mathematical model to estimate global hepatitis B disease burden and vaccination impact. Int J Epidemiol 2005;34:1329–39. [12] Di Bisceglie AM. Hepatitis B and hepatocellular carcinoma. Hepatology 2009;49(May (5 Suppl.)):S56–60.
http://dx.doi.org/10.1016/j.imlet.2015.03.004 0165-2478/© 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.
Letter to the Editor / Immunology Letters 165 (2015) 60–61 [13] Xie H, Song J, Du R, Liu K, Wang J, Tang H, Bai F, Liang J, Lin T, Liu J, Fan D. Prognostic significance of osteopontin in hepatitis B virus-related hepatocellular carcinoma. Dig Liver Dis 2007;39(February (2)):167–72. [14] Wang L, Chen S, Xu K. IL-17 expression is correlated with hepatitis B-related liver diseases and fibrosis. Int J Mol Med 2011;27(March (3)):385–92.
Raffaella Mormile ∗ Division of Pediatrics and Neonatology, Moscati Hospital, Aversa, Italy
61
∗ Correspondence to: Division of Pediatrics and Neonatology, Moscati Hospital, Via A. Gramsci 3, 81031 Aversa, Italy. Tel.: +39 0815001503; mobile: +39 3392045468. E-mail address: [email protected]
8 March 2015 Available online 17 March 2015
Contents lists available at ScienceDirect
Immunology Letters journal homepage: www.elsevier.com/locate/immlet
Letter to the Editor
Hepatitis B virus (HBV) infection and multiple sclerosis: One more reason to undergo vaccination? Over the last two decades extensive research has asked whether there is any link between HB vaccination and the risk of developing MS [1–4]. Most of these publications reported the absence of a link or a slightly increased risk, but not sufficiently significant on the statistical level [2–4]. Recently, a study from France has highlighted a correlation between HB vaccination and MS with the application of Hill’s criteria to the data [4]. However, all this is expected to require further epidemiological studies, particularly from the French health insurance data [3,4]. Therefore, on the basis of the current data, there is no need to modify the vaccination recommendations [2–4]. MS is an inflammatory disease of the central nervous system (CNS) characterized by an autoimmune response against the myelin sheaths and axons, leading to progressive neurological dysfunction with a variable clinical course [5]. An increasing bulk of data suggest that osteopontin (OPN) may be involved in MS development and, especially, progression [5,6]. OPN is an integrin-binding glycoprotein also known as secreted phosphoprotein 1 (SPP1) functioning as a free cytokine in body fluids or as an immobilized extracellular matrix molecule in mineralized tissue [5–7]. OPN has been described to influence the development of several autoimmune diseases through the OPN immunoregulatory effects up-regulating the pro-inflammatory cytokines from both T helper type 1(TH1) and T helper type 17 (TH17) cell pathways [5,6]. It has been shown that OPN transcript is abundant in plaques dissected from brain of patients affected by MS, whereas it is absent in control brain tissue [5,6]. Concordantly, IL-17 secreting TH17 cells have been found to be elevated in MS patients [8]. HB virus infection is a worldwide public health problem of major concern [9,10]. It attacks the liver and can cause both acute and chronic disease including cirrhosis and hepatocellular carcinoma (HCC) with an incidence of 620.000 death per year [9–11]. It has been estimated that approximately 4.5 million new HBV infections occur worldwide each year, of which a quarter progress to liver disease and cirrhosis [10,11]. Vaccination with recombinant Hepatitis B virus surface antigen (HbsAg) is considered as the main valuable strategy for controlling and preventing HBV infection and its long-term serious sequelae, on global scale, both in terms of cost-effectiveness and benefit-cost ratios [10,12]. The implementation of large-scale programs of vaccination against HBV has led to a substantial decrease in disease burden, in the carrier rate and in HBrelated morbidity and mortality [9–11]. Thus, according to the WHO recommendations, universal vaccination has been currently implemented in 168 countries worldwide with an outstanding record of safety and efficacy [9–12]. HCC is one of the most frequent solid tumors occurring worldwide [12]. Chronic infection with HBV has
been connected epidemiologically with the development of HCC for more than 30 years [12]. Interestingly, an increased expression of OPN has been observed in HBV-related HCC [7,13]. The levels of OPN has been closely related to capsular infiltration, venous invasion, lymph node metastatis, and also with worse prognosis, implying that OPN may be a useful molecular marker for predicting the prognosis of HCC [7,13]. Moreover, it has been demonstrated that IL-17 expression is associated with the progression of HBV related chronic liver diseases, especially in the formation of liver fibrosis that is a major link in the development of cirrhosis [14]. With respect to the above, we advance the hypothesis that patients with MS may be at a higher risk of HB-related chronic liver disease, cirrhosis, and HCC as a consequence of the increased expression of both OPN and IL17. Therefore, HB vaccination is especially important for this category of patients. We speculate that HB vaccination should be strongly recommended for children and younger adults who have not been previously vaccinated against HB taking into account that HBV infection is highly contagious and there is no conclusive evidence that HBV vaccination is associated with the risk of MS.
References [1] Ascherio A, Zhang SM, Hernán MA, Olek MJ, Coplan PM, Brodovicz K, Walker AM. Hepatitis B vaccination and the risk of multiple sclerosis. N Engl J Med 2001;344(February (5)):327–32. [2] Hernán MA, Jick SS, Olek MJ, Jick H. Recombinant hepatitis B vaccine and the risk of multiple sclerosis: a prospective study. Neurology 2004;63(September (5)):838–42. [3] Martinez-Sernandez V, Figueiras A. Central nervous system demyelinating diseases and recombinant hepatitis B vaccination: a critical review of scientific production. J Neurol 2013;260:1951–9. [4] Le Houézec D. Evolution of multiple sclerosis in France since the beginning of hepatitis B vaccination. Immunol Res 2014;60(December (2–3)): 219–25. [5] Comi C, Cappellano G, Chiocchetti A, Orilieri E, et al. The impact of osteopontin gene variations on multiple sclerosis development and progression. Clin Dev Immunol 2012;2012:212893. [6] Shimizu Y, Ota K, Ikeguchi R, Kubo S, Kabasawa C, Uchiyama S. Plasma osteopontin levels are associated with disease activity in the patients with multiple sclerosis and neuromyelitis optica. J Neuroimmunol 2013;263(1–2): 148–51. [7] Liang KH, Yeh CT. OPN sesame. Hepatobiliary Surg Nutr 2014;3:112–4. [8] Babaloo Z, Aliparasti M, Babaie F, Almasi S, Baradaran B, Farhoodi M. The role of Th17 cells in patients with relapsing-remitting multiple sclerosis: interleukin17A and interleukin-17F serum levels. Immunol Lett 2015;164(2):76–80. [9] Romano L, Paladini S, Galli C, Raimonido G, Pollicino T, Zanetti AR. Hepatitis B vaccination. Hum Vaccin Immunother 2015;11:53–7. [10] Zanetti AR, Van Damme P, Shouval D. The global impact of vaccination against hepatitis B: a historical overview. Vaccine 2008;26(November (49)): 6266–73. [11] Goldstein ST, Zhou F, Hadler SC, Bell BP, Mast EE, Margolis HS. A mathematical model to estimate global hepatitis B disease burden and vaccination impact. Int J Epidemiol 2005;34:1329–39. [12] Di Bisceglie AM. Hepatitis B and hepatocellular carcinoma. Hepatology 2009;49(May (5 Suppl.)):S56–60.
http://dx.doi.org/10.1016/j.imlet.2015.03.004 0165-2478/© 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.
Letter to the Editor / Immunology Letters 165 (2015) 60–61 [13] Xie H, Song J, Du R, Liu K, Wang J, Tang H, Bai F, Liang J, Lin T, Liu J, Fan D. Prognostic significance of osteopontin in hepatitis B virus-related hepatocellular carcinoma. Dig Liver Dis 2007;39(February (2)):167–72. [14] Wang L, Chen S, Xu K. IL-17 expression is correlated with hepatitis B-related liver diseases and fibrosis. Int J Mol Med 2011;27(March (3)):385–92.
Raffaella Mormile ∗ Division of Pediatrics and Neonatology, Moscati Hospital, Aversa, Italy
61
∗ Correspondence to: Division of Pediatrics and Neonatology, Moscati Hospital, Via A. Gramsci 3, 81031 Aversa, Italy. Tel.: +39 0815001503; mobile: +39 3392045468. E-mail address: [email protected]
8 March 2015 Available online 17 March 2015
