Original Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Aug 21, 2013; 19(31): 5067-5075
Published online Aug 21, 2013. doi: 10.3748/wjg.v19.i31.5067
Serum proteins in chronic hepatitis B patients treated with peginterferon alfa-2b
Sunida Kuakarn, Poorichaya SomParn, Pisit Tangkijvanich, Varocha Mahachai, Visith Thongboonkerd, Nattiya Hirankarn
Sunida Kuakarn, Medical Microbiology, Interdisciplinary Program, Graduate School, Chulalongkorn University, Bangkok 10330, Thailand
Poorichaya SomParn, Nattiya Hirankarn, Immunology Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Pisit Tangkijvanich, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Varocha Mahachai, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Visith Thongboonkerd, Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
Visith Thongboonkerd, Center for Research in Complex Systems Science, Mahidol University, Bangkok 10700, Thailand
Author contributions: Kuakarn S performed the majority of experiments; SomParn P and Thongboonkerd V provided analytical tools and were also involved in editing the manuscript; Tangkijvanich P and Mahachai V provided the collection of samples in addition to providing financial support for this work; Hirankarn N designed the study and wrote the manuscript.
Supported by The 90th Anniversary of Chulalongkorn University Fund (Ratchadaphiseksomphot Endowment Fund); The Thailand Research Fund, No. RMU5180051; The Thailand Research Fund Senior Research Scholarship, No. RTA5380005; The Higher Education Research Promotion and National Research University Project of Thailand, Office of the Higher Education Commission, No. HR1163A; Integrated Innovation Academic Center, Chulalongkorn University Centenary Academic Development Project, No. CU56-HR05, The Liver Research Unit, Chulalongkorn University
Correspondence to: Nattiya Hirankarn, MD, PhD, Immunology Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, 254 Phayathai Road, Pathumwan, Bangkok 10330, Thailand. nattiyap@gmail.com
Telephone: +66-2-2564132   Fax: +66-2-2525952
Received: January 21, 2013
Revised: June 6, 2013
Accepted: June 19, 2013
Published online: August 21, 2013

AIM: To study the differential protein profile in serum of hepatitis B patients.

METHODS: Serum samples were obtained from patients with chronic hepatitis B who were receiving peginterferon alfa-2b. The serum samples were subjected to albumin depletion and analyzed by two-dimensional gel electrophoresis (2-DE). Differentially expressed protein spots were identified by electrospray ionization-quadrupole time-of-flight mass spectrometry. Alpha-2-HS-glycoprotein, complement component C3c and CD5 antigen were further analyzed by an enzyme-linked immunosorbent assay and immunonephelometry.

RESULTS: Nineteen patients with HBeAg-positive chronic hepatitis B (CHB) were studied. These patients were followed for at least 1 year after treatment and were classified according to their treatment response: responders (n = 9) and non-responders (n = 10). 2-DE and MS/MS analysis were performed to compare the serum proteins before initiating peginterferon alfa-2b. From the quantitative analysis of the 2-D gel, 7 proteins were detected between the two groups at different levels before treatment. Among these potential candidates, serum levels of alpha-2-HS-glycoprotein, complement component C3c and CD5 antigen-like precursor were further analyzed. In the validation phase, 23 subjects, 9 sustained responders and 14 non-responders, were recruited. Interestingly, the levels of alpha-2-HS-glycoprotein and complement component C3c were elevated in the serum of the non-responders compared to the responders.

CONCLUSION: Serum alpha-2-HS-glycoprotein and complement component C3c may be potential serum biomarkers in predicting the treatment response of peginterferon alfa-2b in patients with CHB prior to treatment.

Keywords: Proteomics, Peginterferon alfa-2b, Chronic hepatitis B, Alpha-2-HS-glycoprotein, Serum

Core tip: Serum proteins serve as non-invasive biomarkers for several diseases. This is the first report on the potential use of common protein levels in the serum of chronic hepatitis B (CHB) patients to predict treatment responsiveness to peginterferon alfa-2b. We identified 2 potential serum biomarkers, alpha-2-HS-glycoprotein and complement component C3c, that can be used to predict treatment outcome in patients with CHB receiving peginterferon alfa-2b. The identification of these biomarkers prior to treatment is preferable in order to avoid systemic side effects due to interferon therapy.