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IgG3 subclass: A possible trigger of mixed cryoglobulin cascade in hepatitis C virus chronic infection

Umberto Basile1, Francesca Gulli2, Laura Gragnani3

  • 1Department of Laboratory Medicine, Catholic University of the Sacred Heart, Largo A. Gemelli, 8, 00168 Rome, Italy.

Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
|July 10, 2017
PubMed

Insights

Hepatitis C virus (HCV) infection is linked to cryoglobulinemia. This study found distinct IgG subclass patterns in HCV patients, suggesting a progression from polyclonal to monoclonal B-cell proliferation in cryoglobulin formation.

Area of Science:

  • Immunology
  • Virology
  • Hematology

Background:

  • Hepatitis C virus (HCV) is a primary cause of B-lymphocyte proliferation in mixed cryoglobulinemia (MC).
  • Cryoglobulins, proteins that precipitate in cold, are key in MC pathogenesis.
  • Understanding cryoglobulin subclasses in HCV is crucial for MC insights.

Purpose of the Study:

  • To investigate the presence, prevalence, and characteristics of cryoglobulin subclasses in HCV patients.
  • To explore the relationship between IgG subclasses and mixed cryoglobulinemia in HCV.
  • To elucidate the B-cell clonal selection process in HCV-associated cryoglobulinemia.

Main Methods:

  • Fifty HCV-infected patients with cryoglobulins were enrolled.
  • Characterization of IgG subclasses within cryoprecipitate.
  • Determination of serum IgG and IgM Rheumatoid Factor (RF).
  • Stratification of patients based on IgG3 subclass presence.

Main Results:

  • Significant differences in IgM concentration and RF levels were observed between IgG3-positive and IgG3-negative groups.
  • Higher IgM concentration and IgM-RF in the IgG3-negative cohort.
  • Higher IgG-RF in the IgG3-positive group.
  • Monoclonal IgM in IgG3-negative patients correlated with higher cryocrit.
  • C4 levels differed between polyclonal and monoclonal IgM groups.

Conclusions:

  • Cryoglobulins in HCV may represent a progressive clonal selection of B-cells.
  • The process involves initial stimulation of IgG3 production, followed by polyclonal IgM-RF, and potentially monoclonal IgM-RF and IgG3-RF clones.
  • This progression offers insights into the pathogenesis of HCV-associated MC.

Keywords:
IgG subclassesMixed cryoglobulinemiaRheumatoid Factor

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