Abstract
The reference diagnostic method of human abdominal Cystic Echinococcosis (CE) is imaging, particularly ultrasound, supported by serology when imaging is inconclusive. However, current diagnostic tools are neither optimal nor widely available. The availability of a test detecting circulating biomarkers would considerably improve CE diagnosis and cyst staging (active vs inactive), as well as treatments and follow-up of patients. Exosomes are extracellular vesicles involved in intercellular communication, including immune system responses, and are a recognized source of biomarkers. With the aim of identifying potential biomarkers, plasma pools from patients infected by active or inactive CE, as well as from control subjects, were processed to isolate exosomes for proteomic label-free quantitative analysis. Results were statistically processed and subjected to bioinformatics analysis to define distinct features associated with parasite viability. First, a few parasite proteins were identified that were specifically associated with either active or inactive CE, which represent potential biomarkers to be validated in further studies. Second, numerous identified proteins of human origin were common to active and inactive CE, confirming an overlap of several immune response pathways. However, a subset of human proteins specific to either active or inactive CE, and central in the respective protein-protein interaction networks, were identified. These include the Src family kinases Src and Lyn, and the immune-suppressive cytokine TGF-β in active CE, and Cdc42 in inactive CE. The Src and Lyn Kinases were confirmed as potential markers of active CE in totally independent plasma pools. In addition, insights were obtained on immune response profiles: largely consistent with previous evidence, our observations hint to a Th1/Th2/regulatory immune environment in patients with active CE and a Th1/inflammatory environment with a component of the wound healing response in the presence of inactive CE. Of note, our results were obtained for the first time from the analysis of samples obtained in vivo from a well-characterized, large cohort of human subjects.
Highlights
Cystic echinococcosis (CE) is a parasitic zoonosis caused by the cystic larval stage of the dog tapeworm Echinococcus granulosus sensu lato
In this study we carried out a proteomic analysis of the exosomes circulating in the plasma of CE infected individuals, with either active (AP) or inactive CE (IP), and control subjects (Ctr), to identify potential biomarkers of CE infection and metacestode viability, and further to investigate the pathogen-host interplay communications
All CE patients screened in the HERACLES project survey [29, 30] were carefully characterized by US imaging and transitional cyst cases, patients under current or recent treatments, and patients with multiple cyst not classifiable in a clear-cut manner were excluded from the study
Summary
Cystic echinococcosis (CE) is a parasitic zoonosis caused by the cystic larval stage (metacestode) of the dog tapeworm Echinococcus granulosus sensu lato. The global burden of human CE has been estimated in more than 1 million people infected, with over 1 million DALYs lost every year, when accounting for underreporting [1]. The parasite is transmitted between canid definitive hosts (mainly dogs) and intermediate hosts (mainly livestock, in particular sheep) through the fecal-oral route. CE is globally distributed, in particular in rural areas where livestock breeding practices maintain the life cycle of the parasite [3]. Up to 10% of infections may cause serious, disabling or even fatal disease, especially in case of complications, dissemination, or involvement of organs such as the central nervous system or the bones [4].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
