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

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

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Department of Neuroscience, Biomedical and Metabolic Sciences, University of Modena and Reggio Emilia, Modena 41125, Italy.
Rheumatology Unit, University of Modena and Reggio Emilia, Modena 41124, Italy.
Rheumatology Unit, University of Modena and Reggio Emilia, Modena 41124, Italy,
Institute for Advanced Sciences Convergence and International Clean Water Institute, Herndon, VA 20171, USA.



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.


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


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.


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).


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


Aetiopathogenesis; HCV; cryoglobulinemic vasculitis; microparticles; nanoparticles.

[Indexed for MEDLINE]

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