Serum Biomarker Signature Identifies Patients With B-cell non-Hodgkin Lymphoma Associated With Cryoglobulinemia Vasculitis in Chronic HCV Infection

Autoimmun Rev. 2014 Mar;13(3):319-26. doi: 10.1016/j.autrev.2013.11.001. Epub 2013 Nov 9.


Background: Hepatitis C virus (HCV) is associated with B-cell disorders, including mixed cryoglobulinemia (MC) and B-cell non-Hodgkin lymphoma (B-NHL). We hypothesized that combination of serum biomarkers could be used to identify B-NHL in HCV patients.

Methods: We measured in 155 HCV infected patients, with and without MC and/or B-NHL, serum levels of eight markers previously described to be increased in patients with B-NHL, i.e. sCD22, sCD27, sIL-2Rα, sCD137, free-light chains of Ig (ratio κ/λ), heavy chains of Ig (ratio IgMκ/IgMλ), gammaglobulins and C4. We used a multiparametric analysis to determine a signature that identifies patients with overt B-NHL.

Results: Serum levels were significantly different between patients without MC, patients with asymptomatic MC, patients with MC vasculitis and those with MC vasculitis and B-NHL for all biomarkers except for sCD137. Using multiparametric analysis, we identified a signature involving sCD27, sIL-2Rα, gammaglobulins and C4 levels associated with the presence of overt B-NHL in HCV-infected patients. This signature had a sensitivity of 100%, a specificity of 90%, and positive and negative predictive values of 97 and 100%, respectively for discriminating patients with overt B-NHL and those without B-NHL.

Conclusion: Our data indicate that serum biomarker signature allows identifying HCV-infected patients presenting with overt B-NHL.

Keywords: B-cell non-Hodgkin lymphoma; Biomarkers; Hepatitis C virus; Mixed cryoglobulinemia; Soluble IL-2Rα.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers / blood
  • Cryoglobulinemia / blood*
  • Cryoglobulinemia / etiology
  • Cryoglobulinemia / pathology
  • Hepatitis C, Chronic / blood*
  • Hepatitis C, Chronic / complications
  • Humans
  • Lymphoma, B-Cell / blood*
  • Lymphoma, B-Cell / etiology
  • Lymphoma, Non-Hodgkin / blood*
  • Lymphoma, Non-Hodgkin / etiology
  • Vasculitis / blood*
  • Vasculitis / etiology


  • Biomarkers