Abstract
Paroxysmal Nocturnal Hemoglobinuria (PNH) is a clonal disease of blood cells caused by the lack of glycosyl phosphatidyl inositol anchored proteins bound to the cell membrane. In consequence, erythrocytes lead to intravascular hemolysis upon complement activation, which promotes high risk of thrombosis, intravascular hemolytic anemia, and bone marrow failure in patients. The mechanisms of thrombosis in PNH are still poorly understood. Treatment with eculizumab reduces intravascular hemolysis and thrombotic risk, but not in all cases. Exosomes are extracellular vesicles released by cells and whose secretion is closely related to the inflammatory status. They participate in cell communication by activating signaling pathways and transferring genetic material and proteins to host cells. In consequence, exosomes may serve as surrogate biomarkers for the prognosis and/or diagnosis of a disease. Isolation of exosomes was carried out from healthy controls and from three groups of PNH patients, i.e. i) with no eculizumab treatment; ii) under treatment with eculizumab that have not suffered thrombosis; and iii) under treatment with eculizumab but that have suffered thrombosis. The miRNAome and proteome was analyzed using plasma focus miRNAs PCR panel and LC-MS analysis respectively. We found differential expression of miRNAs miR-148b-3p, miR-423-3p, miR29b-3p, miR15b-5p, let-7e-5p, miR126-3p, miR-125b-5p and miR-376c-3p as well as hemoglobin, haptoglobin, protein S and C4-binding protein in healthy controls vs PNH patients. Our results warrant further research and provide new information on the content of exosomes that could play a role in the hypercoagulable state in this disease.
Highlights
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, systemic disease associated with the deficiency of certain proteins in the erythrocyte membrane[1]
There are multiple factors that contribute to the onset of the thrombotic event, it is likely that platelet activation is the main cause of the high incidence of thrombosis associated with PNH3
They could participate in hematological disorders such as PNH, since it is a disease associated with thrombosis and inflammation, and is related to an increasing number of extracellular vesicles released into the plasma[11]
Summary
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, systemic disease associated with the deficiency of certain proteins in the erythrocyte membrane[1]. The fact that the composition of the exosome is a reflection of the physiological state has confirmed that exosomes could be considered biomarkers for the diagnosis and prognosis of different diseases[9,10] They could participate in hematological disorders such as PNH, since it is a disease associated with thrombosis and inflammation, and is related to an increasing number of extracellular vesicles released into the plasma[11]. Our objective here was to evaluate the differential miRNA and the proteome profile of the plasma exosomes of patients with PNH versus those of healthy subjects This new insight could help identify surrogate biomarkers for the diagnosis and prognosis of PNH and better understand the mechanisms of underlying thrombosis in this rare disease
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