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  • Mixed Cryoglobulinemia is a combination of both types II and III.
  • Mixed CGs is associated with following conditions:
    • SLE (systemic lupus erythematous)
    • Sjögren's syndrome,
    • HCV
    • Lymphoproliferative disorders
  • Al the above mentioned disorders can cause excessive production of B-cell which can further lead to selective expansion of Cryoglobulinemia producing B-cell clones.
  • In HCV infected patients the HCV complexes such as HCV-IgG, HCV-lipoprotein cause B-cell hyper-proliferation through the CD81 leading to expansion of specific B-cell clones such as WA idiotype or V(H)1-69.
  • HCV particles are often found in such patients' serum CG complexes, but, at the same time, CG development in hepatitis C infection does not directly require the HCV virion or its components [38]. In this sense, CG development may, in fact, reflect a normal, expected response to regulate immune complexes in states of chronic immune activation.
  • Among patients with HCV infection, the number of circulating T cells with surface markers compatible with a suppressor phenotype may be a feature that differs between patients with cryoglobulinemic vasculitis and those with asymptomatic CG.
  • This was illustrated in a study that compared the percentage of "regulatory" T cells in 69 patients with HCV infection who had symptomatic CG with others with asymptomatic HCV infection [39].
  • The mean levels of regulatory T cells were significantly lower in those with symptomatic HCV-associated CG than asymptomatic subjects (2.6 versus 7.4 percent, respectively).
  • Whether the diminished proportion of regulatory T cells plays a role in causing vasculitis is uncertain but warrants further exploration.