Micro and nanoparticles as possible pathogenetic co-factors in mixed cryoglobulinemia

Occup Med (Lond). 2017 Jan;67(1):64-67. doi: 10.1093/occmed/kqw134. Epub 2016 Sep 30.


Background: Mixed cryoglobulinemia (MC) is a rare multisystem disease whose aetiopathogenesis is not completely understood. Hepatitis C virus (HCV) infection may have a causative role, and genetic and/or environmental factors may also contribute.

Aims: To investigate the presence and possible role of environmental agents in MC.

Methods: We recruited 30 HCV-infected MC patients with different clinical manifestations and a control group of 30 healthy, sex-/age-matched volunteers. We collected serum samples from each patient and incubated at 4°C for 7 days to obtain cryoprecipitate samples. We used environmental scanning electron microscopy (ESEM) and energy dispersive X-ray spectroscopy microanalysis to verify the presence of microparticles (MPs) and nanoparticles (NPs) in serum and cryoprecipitate samples. We evaluated environmental exposure using a medical and occupational history questionnaire for each subject.

Results: MC patients had a significantly higher risk of occupational exposure (OR 5.6; 95% CI 1.84-17.50) than controls. ESEM evaluation revealed a significantly higher concentration, expressed as number of positive spots (NS), of serum inorganic particles in MC patients compared with controls (mean NS 18, SD = 16 versus NS 5.4, SD = 5.1; P < 0.05). Cryoprecipitate samples of MC patients showed high concentrations of inorganic particles (mean NS 49, SD = 19). We found a strong correlation between NS and cryocrit (i.e. percentage of cryoprecipitate/total serum after centrifugation at 4°C) levels (P < 0.001).

Conclusions: In addition to HCV infection, MPs and NPs might play an important role in the aetiopathogenesis of MC.

Keywords: Aetiopathogenesis; HCV; cryoglobulinemic vasculitis; microparticles; nanoparticles..

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cryoglobulinemia / blood
  • Cryoglobulinemia / diagnosis
  • Cryoglobulinemia / physiopathology*
  • Female
  • Hepacivirus / pathogenicity
  • Hepatitis C / blood
  • Hepatitis C / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Nanoparticles / analysis*
  • Virulence Factors / blood*


  • Virulence Factors