Skip to main content
PMC home page
Virologica Sinica logoLink to Virologica Sinica
. 2015 Jul 23;30(4):249–260. doi: 10.1007/s12250-015-3605-4

Serum ficolin-2 concentrations are significantly changed in patients with hepatitis B virus infection and liver diseases

Tielong Chen 1,2, Yilan Hu 1,3, Quanquan Ding 1, Jing Yu 4, Fubing Wang 2, Fengling Luo 1,✉, Xiao-Lian Zhang 1,✉
PMCID: PMC8200881  PMID: 26220728

Abstract

Human ficolin-2 is an important lectin complement pathway activator that is secreted from liver cells and has been implicated as an anti-infection innate immune molecule. However, the role of ficolin-2 protein and its dynamic changes over the course of and in the prognosis of chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) remain unclear. In this study, we analyzed ficolin-2 protein expression in a cohort of individuals with CHB infection, HCC and cirrhosis. A sandwich enzyme-linked immunosorbent assay (ELISA) method was used to measure serum ficolin-2 concentrations. Ficolin-2 expression in liver tissues was detected by immunohistochemical staining. Serum ficolin-2 concentrations in CHB patients were significantly higher than in healthy controls and HBV carriers. After 48 weeks of routine amelioration liver function treatment, serum ficolin-2 concentrations decreased and were positively correlated with favorable alanine aminotransferase (ALT), HBV DNA and HBeAg-seroconversion outcomes. Interestingly, we observed much lower expression of serum and intrahepatic ficolin-2 in HCC and cirrhosis compared with healthy controls. Our findings suggest that serum and intrahepatic ficolin-2 levels may be considered one of the indicators for the response of chronic HBV infection, HCC and cirrhosis.

graphic file with name 12250_2015_3605_Fig1_HTML.jpg

Keywords: ficolin-2, chronic hepatitis B (CHB), hepatocellular carcinoma (HCC)

Footnotes

ORCID: 0000-0003-0826-7327

ORCID: 0000-0002-8283-9381

Contributor Information

Fengling Luo, Phone: +86-13517210062, FAX: +86-27-68759986, Email: fengling810810@163.com.

Xiao-Lian Zhang, Phone: +86-27-68759986, FAX: +86-27-68759986, Email: zhangxiaolian@whu.edu.cn.

References

  1. Brown KS, Keogh MJ, Tagiuri N, Grainge MJ, Presanis JS, Ryder SD, Irving WL, Ball JK, Sim RB, Hickling TP. Severe fibrosis in hepatitis C virus-infected patients is associated with increased activity of the mannan-binding lectin (MBL)/MBL-associated serine protease 1 (MASP-1) complex. Clin Exp Immunol. 2007;147:90–98. doi: 10.1111/j.1365-2249.2006.03264.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology. 1994;19:1513–1520. doi: 10.1002/hep.1840190629. [DOI] [PubMed] [Google Scholar]
  3. Dunkelberger JR, Song WC. Complement and its role in innate and adaptive immune responses. Cell Res. 2010;20:34–50. doi: 10.1038/cr.2009.139. [DOI] [PubMed] [Google Scholar]
  4. Eisen DP, Minchinton RM. Impact of mannose-binding lectin on susceptibility to infectious diseases. Clin Infect Dis. 2003;37:1496–1505. doi: 10.1086/379324. [DOI] [PubMed] [Google Scholar]
  5. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142:1264–1273. doi: 10.1053/j.gastro.2011.12.061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Endo Y, Sato Y, Matsushita M, Fujita T. Cloning and characterization of the human lectin P35 gene and its related gene. Genomics. 1996;36:515–521. doi: 10.1006/geno.1996.0497. [DOI] [PubMed] [Google Scholar]
  7. Esmat S, Omran D, Sleem GA, Rashed L. Serum mannan-binding lectin in egyptian patients with chronic hepatitis C: its relation to disease progression and response to treatment. Hepat Mon. 2012;12:259–264. doi: 10.5812/hepatmon.5861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. European Association for the Study of the Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol. 2012;57:167–185. doi: 10.1016/j.jhep.2012.02.010. [DOI] [PubMed] [Google Scholar]
  9. Hoang TV, Toan NL, le Song H, Ouf EA, Bock CT, Kremsner PG, Kun JF, Velavan TP. ficolin-2 levels and FCN2 haplotypes influence hepatitis B infection outcome in Vietnamese patients. PLoS One. 2011;6:e28113. doi: 10.1371/journal.pone.0028113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Holmskov U, Thiel S, Jensenius JC. Annu Rev Immunol. 2003. Collections and ficolins: humoral lectins of the innate immune defense; p. 21. [DOI] [PubMed] [Google Scholar]
  11. Honore C, Rorvig S, Hummelshoj T, Skjoedt MO, Borregaard N, Garred P. Tethering of ficolin-1 to cell surfaces through recognition of sialic acid by the fibrinogen-like domain. J Leukoc Biol. 2010;88:145–158. doi: 10.1189/jlb.1209802. [DOI] [PubMed] [Google Scholar]
  12. Hu YL, Luo FL, Fu JL, Chen TL, Wu SM, Zhou YD, Zhang XL. Early increased ficolin-2 concentrations are associated with severity of liver inflammation and efficacy of anti-viral therapy in chronic hepatitis C patients. Scand J Immunol. 2013;77:144–150. doi: 10.1111/sji.12014. [DOI] [PubMed] [Google Scholar]
  13. Hummelshoj T, Munthe-Fog L, Madsen HO, Fujita T, Matsushita M, Garred P. Polymorphisms in the FCN2 gene determine serum variation and function of ficolin-2. Hum Mol Genet. 2005;14:1651–1658. doi: 10.1093/hmg/ddi173. [DOI] [PubMed] [Google Scholar]
  14. Hummelshoj T, Munthe-Fog L, Madsen HO, Garred P. Functional SNPs in the human ficolin (FCN) genes reveal distinct geographical patterns. Mol Immunol. 2008;45:2508–2520. doi: 10.1016/j.molimm.2008.01.003. [DOI] [PubMed] [Google Scholar]
  15. J Gastroenterol Hepatol. 2008.
  16. Kilpatrick DC, Delahooke TE, Koch C, Turner ML, Hayes PC. Mannan-binding lectin and hepatitis C infection. Scand J Gastroenterol. 2003;132:92–95. doi: 10.1046/j.1365-2249.2003.02122.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Li J, Wu W, Peng G, Chen F, Bai M, Zheng M, Chen Z. HBcAg induces interleukin-10 production, inhibiting HBcAg-specific Th17 responses in chronic hepatitis B patients. Immunol Cell Biol. 2010;88:834–841. doi: 10.1038/icb.2010.63. [DOI] [PubMed] [Google Scholar]
  18. Liu J, Ali MA, Shi Y, Zhao Y, Luo F, Yu J, Xiang T, Tang J, Li D, Hu Q, Ho W, Zhang X. Specifically binding of L-ficolin to N-glycans of HCV envelope glycoproteins E1 and E2 leads to complement activation. Cell Mol Immunol. 2009;6:235–244. doi: 10.1038/cmi.2009.32. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Liu Y, Endo Y, Iwaki D, Nakata M, Matsushita M, Wada I, Inoue K, Munakata M, Fujita T. J Immunol. 2005. Human M-ficolin is a secretory protein that activates the lectin complement pathway; pp. 3150–3156. [DOI] [PubMed] [Google Scholar]
  20. Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association, Severe Liver Diseases and Artificial Liver Group, Chinese Society of Hepatology, Association CM. 2006. Diagnostic and treatment guidelines for liver failure. Zhonghua Gan Zang Bing Za Zhi, 14: 643–646. (In Chinese) [PubMed]
  21. Mannan R, Misra V, Misra SP, Singh PA, Dwivedi M. A comparative evaluation of scoring systems for assessing necro-inflammatory activity and fibrosis in liver biopsies of patients with chronic viral hepatitis. J Clin Diagn Res. 2014;8:08–12. doi: 10.7860/JCDR/2014/8704.4718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Matsushita M, Endo Y, Taira S, Sato Y, Fujita T, Ichikawa N, Nakata M, Mizuochi T. A novel human serum lectin with collagen- and fibrinogen-like domains that functions as an opsonin. J Biol Chem. 1996;271:2448–2454. doi: 10.1074/jbc.271.5.2448. [DOI] [PubMed] [Google Scholar]
  23. Pan Q, Chen H, Wang F, Jeza VT, Hou W, Zhao Y, Xiang T, Zhu Y, Endo Y, Fujita T. L-Ficolin Binds to the Glycoproteins Hemagglutinin and Neuraminidase and Inhibits Influenza A Virus Infection Both in vitro and in vivo. J Innate Immun. 2012;4:312–324. doi: 10.1159/000335670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Poynard T, Yuen MF, Ratziu V, Lai CL. Viral hepatitis C. Lancet. 2003;362:2095–2100. doi: 10.1016/S0140-6736(03)15109-4. [DOI] [PubMed] [Google Scholar]
  25. Ren Y, Ding Q, Zhang X. Ficolins and infectious diseases. Virol Sin. 2014;29:25–32. doi: 10.1007/s12250-014-3421-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Song WC, Sarrias MR, Lambris JD. Complement and innate immunity. Immunopharmacology. 2000;49:187–198. doi: 10.1016/S0162-3109(00)80303-3. [DOI] [PubMed] [Google Scholar]
  27. Sugimoto R, Yae Y, Akaiwa M, Kitajima S, Shibata Y, Sato H, Hirata J, Okochi K, Izuhara K, Hamasaki N. Cloning and characterization of the Hakata antigen, a member of the ficolin/opsonin p35 lectin family. J Biol Chem. 1998;273:20721–20727. doi: 10.1074/jbc.273.33.20721. [DOI] [PubMed] [Google Scholar]
  28. Walport MJ. Complement. First of two parts. N Engl J Med. 2001;344:1058–1066. doi: 10.1056/NEJM200104053441406. [DOI] [PubMed] [Google Scholar]
  29. Wang H, Xue L, Yan R, Zhou Y, Wang MS, Cheng MJ, Hai-Jun H. Comparison of histologic characteristics of Chinese chronic hepatitis B patients with persistently normal or mildly elevated ALT. PLoS One. 2013;8:e80585. doi: 10.1371/journal.pone.0080585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Zhao Y, Ren Y, Zhang X, Zhao P, Tao W, Zhong J, Li Q, Zhang XL. ficolin-2 inhibits hepatitis C virus infection, whereas apolipoprotein E3 mediates viral immune escape. J Immunol. 2014;193:783–796. doi: 10.4049/jimmunol.1302563. [DOI] [PubMed] [Google Scholar]

Articles from Virologica Sinica are provided here courtesy of Wuhan Institute of Virology, Chinese Academy of Sciences

RESOURCES