Differential cytokine network profile in polycythemia vera and secondary polycythemia

Abstract

Polycythemia vera (PV) is a clonal disorder resulting from neoplastic transformation of hematopoietic stem cells, while secondary polycythemia (SP) is a disease characterized by increased absolute red blood cell mass caused by stimulation of red blood cell production. Although the physiopathology of SP and PV is distinct, patients with these diseases share similar symptoms. The early differential diagnosis may improve the quality of life and decrease the disease burden in PV patients, as well as enable curative treatment for SP patients. PV is considered an oncoinflammatory disease because PV patients exhibit augmented levels of several pro-inflammatory cytokines. In this sense, we examined whether analysis of the cytokine production profile of SP and PV patients would help to distinguish them, despite their clinical similarities. Here we reported that SP patients exhibited decreased plasma levels of, IL-17A, IFN-γ, IL-12p70 and TNF-α when compared with PV patients, suggesting that analysis of the cytokine production profile may be an useful diagnostic biomarker to distinguish PV from SP patients. Polycythemia vera (PV) and secondary polycythemia (SP) are hematological diseases characterized by erythropoiesis exacerbation. PV patients present clonal expansion of the hematopoietic erythroid progenitor and, to a lesser extent, leukocytosis and/or thrombocytosis 1. PV affects more women than men, has an incidence of 0.68-2.6 for every 100,000 individuals per year, and is uncommon in patients younger than 60 years. PV patients have life expectancy of 14 years after diagnosis, and their major risk factors for mortality are thrombotic events and leukemic transformation 2,3. The augmented levels of pro-inflammatory cytokines in PV patients give this neoplasm the status of oncoinflammatory disease 4-6. Secondary polycythemia (SP) is a poorly understood clinical entity. The SP prevalence is considerably high, but it is hard to quantify due to the variety of causes and scarcity of data 7. Compared with PV patients, SP patients have lower overall survival 8,9 and higher morbidity and mortality rates, as demonstrated by small non-randomized studies. In spite of the epidemiological evidence, it is not clear whether the high mortality rate is associated with the increased red blood cell volume. To date, no randomized studies were conducted to analyze whether the morbidity and/or mortality rates in SP patients correlate with the increased red blood cell volume and thrombosis 7. SP can be congenital, caused by erythropoietin (EPO) receptor mutations, or acquired and induced by physiological changes that raise the body demand for oxygen, such as renal, lung and heart disease, high altitudes, severe obesity, defective oxygen transport, and EPO overproduction caused by certain kidney diseases or secretion by some tumors 8-10. The increment in erythrocyte mass in SP patients results from bone marrow stimulation by EPO or abnormal functioning of the mutant EPO receptor. In contrast to PV patients, SP patients do not have increased le...

Blocking the CD47-SIRPα interaction reverses the disease phenotype in a polycythemia vera mouse model

“…Our findings further indicate that CD47 blockade leads to an expansion of phenotypically phagocytic MerTK+ splenic Mdcs in PV mice, which derive from monocytes. It has been shown that IFNγ and GM-CSF, which are increased in PV patients [ 36 ], can guide the transition of monocytes into Mdcs in experimental autoimmune encephalomyelitis, a model of tissue inflammation [ 8 ]. We, therefore, postulate that in our model, the addition of anti-CD47 further increases cytokine production, leading to the differentiation of Ly6C hi monocytes into Mdcs [ 7 , 37 ].…”

Rationale and design of the multicentric, double-blind, double-placebo, randomized trial APrepitant versus HYdroxyzine in association with cytoreductive treatments for patients with myeloproliferative neoplasia suffering from Persistent Aquagenic Pruritus. Trial acronym: APHYPAP

“…Recently, two studies from Da Costa Cacemiro et al shown (1) a higher rate of some cytokines and chemokines in MPN patients (PV, ET, and MF) as in healthy subjects, (2) a different cytokinic profile between the different MPNs that permits to help the differential diagnosis between PV and secondary polycythemia, and (3) that the mutational status (JAK2V617F + or −) had also an impact on the expression profile of cytokines [ 31 ]. Among these profiles described in the different MPNs, IL-1β, IL-4, IL-6, IL-10, IL-17A, and IFN-γ released by Th17 have been found [ 32 , 38 ].…”

Electrochemical Nanobiosensors as Point‐of‐Care Testing Solution to Cytokines Measurement Limitations

“…There are also approaches to characterize the blood‐related chronic course diseases as a cytokine level‘s function [57]. For instance, by the use of a 12‐plexed assay, a study showed that it was possible to discriminate the similar symptoms of patients with secondary polycythemia (SP) and polycythemia vera (PV) from the fact that SP patients showed decreased plasma levels of the IL‐17A, IFNγ, IL‐12p70 and TNF‐α oncoinflammatory factors, in comparison to PV patients [86]. In contrast, a 25‐plexed bead array done with blister fluids from patients with complex regional pain syndrome type 1 failed to detect several cytokines (e. g., IL‐1β, IL‐2, IL‐5, IL‐7, IL‐15, IFNγ) that were detected by more sensitive ELISA kits [87].…”