Regulatory B Cells and Their Cytokine Profile in HCV-Related Hepatocellular Carcinoma: Association with Regulatory T Cells and Disease Progression
Helal F. Hetta,
Mohamed A. Mekky,
Asmaa M. Zahran,
Mohamed O. Abdel-Malek,
Haidi K. Ramadan,
Engy A. Shafik,
Wael A. Abbas,
Muhammad Abbas El-Masry,
Nahed A. Mohamed,
Amira A. Kamel,
Najat Marraiki,
Amany Magdy Beshbishy,
Gaber El-Saber Batiha,
Heba A. Osman,
Gopala Koneru,
Mohamed A. El-Mokhtar
Affiliations
Helal F. Hetta
Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0595, USA
Mohamed A. Mekky
Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
Asmaa M. Zahran
Department of Clinical Pathology, South Egypt Cancer Institute, Assiut University, Assiut 71515, Egypt
Mohamed O. Abdel-Malek
Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
Haidi K. Ramadan
Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
Engy A. Shafik
Department of Clinical Pathology, South Egypt Cancer Institute, Assiut University, Assiut 71515, Egypt
Wael A. Abbas
Department of Internal Medicine, Gastroenterology Division, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
Muhammad Abbas El-Masry
Department of Internal Medicine, Gastroenterology Division, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
Nahed A. Mohamed
Department of Medical Biochemistry, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
Amira A. Kamel
Department of Medical Biochemistry, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
Najat Marraiki
Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
Amany Magdy Beshbishy
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2-13, Inada-cho, Obihiro 080-8555, Hokkaido, Japan
Gaber El-Saber Batiha
Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicines, Damanhour University, Damanhur 22511, Egypt
Heba A. Osman
Tropical Medicine and Gastroenterology Department, Hepatology Division, Faculty of Medicine, South Valley University, Qena 83523, Egypt
Gopala Koneru
Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0595, USA
Mohamed A. El-Mokhtar
Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
Although regulatory B cells (Bregs) have been proven to play a suppressive role in autoimmune diseases, infections and different tumors, little is known regarding hepatocellular carcinoma (HCC), especially in hepatitis C-related settings. Herein, we analyzed the frequency of circulating Bregs, serum levels of IL-10, IL-35 and B-cell activating factor (BAFF) and investigated their association with regulatory T cells (Tregs) and disease progression in HCV-related HCC. For comparative purposes, four groups were enrolled; chronic HCV (CHC group, n = 35), HCV-related liver cirrhosis (HCV-LC group, n = 35), HCV-related HCC (HCV-HCC group, n = 60) and an apparently healthy control (Control-group, n = 20). HCC diagnosis and staging were in concordance with the Barcelona Clinic Liver Cancer (BCLC) staging system. Analysis of the percentage of Breg cells and peripheral lymphocyte subsets (Treg) was performed by flow cytometry. Serum cytokine levels of IL-10, IL-35 and B-cell activating factor (BAFF) were measured by ELISA. The frequency of Bregs was significantly higher in the HCV-HCC group compared to the other groups and controls. A significant increase was noted in late-HCC versus those in the early stages. The frequency of Bregs was positively correlated with Tregs, serum IL-10, IL-35 and BAFF. In conclusion, Peripheral Bregs were positively correlated with the frequency of Tregs, IL-10, IL-35 and BAFF, and may be associated with HCV-related HCC progression.
