CD5/CD20 expression on circulating B cells in HCV-related chronic hepatitis and mixed cryoglobulinemia


      • 3 B cell phenotypes were evaluated in HCV+ patients with and w/o MC, and controls.
      • HCV infection was associated with a higher frequency of CLL-like pattern.
      • CLL-like B cells progressively increased from HCV+ MC- to HCV+ MC+ patients.
      • CLL-like B cells also characterized patients with persisting MC despite SVR.
      • CLL-like B cells could identify HCV+ patients at risk for MC or malignant evolution.


      The role of CD5+ B cells in patients with HCV infection and HCV-related disorders, including mixed cryoglobulinemia (MC), has been addressed in previous reports with conflicting results. We established a correlation between CD5/CD20 expression on circulating B lymphocytes, characterizing monoclonal B cell lymphocytosis (MBL), and clinical features in a cohort of 45 patients with chronic HCV hepatitis [without MC: 23 patients (MC- group); with MC: 22 patients (MC+ group)], and 45 HCV-negative healthy subjects as controls. By flow cytometry analysis, three B cells phenotypes were singled out: 1) CD5+CD20dim (CLL-like phenotype); 2) CD5+CD20bright (atypical phenotype); and 3) CD5-CD20+ phenotype. CD5+CD20bright cells were reduced in MC- patients (p=0.049). CD5+CD20dim B cells were significantly higher in group B than in the control group (p=0.003). ROC curve analysis in MC+ patients showed the highest positive likelihood ratio at ≥7.35% (p=0.008) for CLL-like phenotype and at ≤63.6% (p=0.03) for the CD5-CD20+ B cell phenotype. HCV infection was associated with a higher frequency of CLL-like (odds ratio=16, p=0.002) and a lower frequency of atypical (odds ratio: 3.1, p=0.02) and CD5-CD20+ (odds ratio: 11, p=0.01) phenotypes. The association with higher levels of CLL-like phenotype progressively increased from group of MC- patients (odds ratio: 9.3, p=0.04) to the group of MC+ patients (odds ratio: 25.1, p=0.0003).


      The occurrence of a CLL-like pattern may allow to identify HCV-infected patients at risk of developing MC and eventually non-Hodgkin lymphoma, who should require a closer surveillance and a longer follow-up.



      AID (autoimmune disease), aOR (adjusted odds ratio), B-CLL (B cell chronic lymphocytic leukemia), B-NHL (B cell non-Hodgkin lymphoma), BSA (bovine serum albumin), CH (chronic hepatitis), CMV (cytomegalovirus), DAAs (direct-acting antiviral agents), HBV (hepatitis B virus), HCV (hepatitis C virus), HIV (human immunodeficiency virus), IFN (interferon), MBL (monoclonal B cell lymphocytosis), MC (mixed cryoglobulinemia), OR (odds ratio), PBS (phosphate-buffered saline solution), RF (rheumatoid factor), ROC (receiver operating characteristic), SD (standard deviation), SVR (sustained virological response), TCR (T cell receptor.)
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