Impact of deranged B cell subsets distribution in the development of HCV-related cirrhosis and HCC in type two diabetes mellitus

Sci Rep. 2020 Nov 23;10(1):20383. doi: 10.1038/s41598-020-77416-0.

Abstract

Type II diabetes (T2D) may worsen the course of hepatitis C virus infection with a greater risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). In chronic viral infections, the deranged B cell subset signifies uncontrolled disease. The study aimed to verify the relation between B cell subsets' distribution and liver disease progression in chronic hepatitis C (CHC) patients with T2D. A total of 67 CHC patients were divided into two groups; 33 non-diabetic and 34 with T2D. Each group was subdivided into CHC-without LC or HCC (N-CHC), CHC-with LC (CHC-LC), and CHC-with HCC (CHC-HCC). Twenty-seven healthy individuals also participated as controls. Flow cytometry was used to analyze CD19+ B cell subsets based on the expression of CD24 and CD38. CD19+CD24hiCD38hi Immature/transitional B cells elevated in diabetic than non-diabetic patients. In diabetic patients, while CD19+CD24+CD38- primarily memory B cells were higher in CHC-N and CHC-HCC groups than LC with a good predictive accuracy of LC, the opposite was observed for CD19+CD24-CD38- new memory B cells. Only in diabetic patients, the CD19+CD24intCD38int naïve mature B cells were high in CHC-HCC patients with good prognostic accuracy of HCC. Merely in diabetic patients, several correlations were observed between B cell subsets and liver function. Immature/transitional B cells increase remarkably in diabetic CHCpatients and might have a role in liver disease progression. Memory and Naïve B cells are good potential predictors of LC and HCCin diabetic CHCpatients, respectively. Further studies are needed to investigate the role of the CD19+CD24-CD38- new memory B cells in disease progression in CHC patients.

MeSH terms

  • ADP-ribosyl Cyclase 1 / genetics
  • ADP-ribosyl Cyclase 1 / immunology
  • Adult
  • Aged
  • Antigens, CD19 / genetics
  • Antigens, CD19 / immunology
  • B-Lymphocyte Subsets / classification
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / pathology*
  • B-Lymphocyte Subsets / virology
  • CD24 Antigen / genetics
  • CD24 Antigen / immunology
  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / pathology*
  • Carcinoma, Hepatocellular / virology
  • Case-Control Studies
  • Diabetes Mellitus, Type 2
  • Female
  • Gene Expression
  • Hepacivirus / growth & development
  • Hepacivirus / pathogenicity*
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / immunology
  • Hepatitis C, Chronic / pathology*
  • Hepatitis C, Chronic / virology
  • Humans
  • Immunologic Memory
  • Immunophenotyping
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / immunology
  • Liver Cirrhosis / pathology*
  • Liver Cirrhosis / virology
  • Liver Neoplasms / etiology
  • Liver Neoplasms / immunology
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / virology
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Middle Aged

Substances

  • Antigens, CD19
  • CD19 molecule, human
  • CD24 Antigen
  • CD24 protein, human
  • Membrane Glycoproteins
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1