Szlendak U, Krzymieniewska B, Mendek-Czajkowska E, et al. - In paroxysmal nocturnal hemoglobinuria (PNH), the presence of apoptotic and PI(3,4,5)P3 (phosphatidylinositol (3,4,5)-trisphosphate) imbalance in PNH CD34+ cells driven by anti-apoptotic cytokine biosignature is suggested. A therapeutic target in PNH could be afforded by plasma cytokines and intracellular enzymes that regulate the phosphoinositide pathways.

• In this study of 19 patients with PNH and 31 healthy controls, plasma levels of beta chemokines and cytokines were obtained from participants.

• Cytokine biosignature for PNH exist in patients’ plasma.

• A significant elevation in plasma level of MIP-1alpha (macrophage inflammatory protein-1 alpha)/CCL3, eotaxin/CCL11, MCP1/CCL2, IL4 and G-CSF, was observed in the PNH group vs controls.

• PNH patients exhibited a significant decrease in RANTES(regulated upon activation normal T cell expressed and secreted protein)/CCL5, MIP-1beta/CCL4, PDGF-BB and IL9 levels.

• CCL3 was found to be strongly linked with the anti-apoptotic phenotype of stem cells with PNH defect.

• CCL5, CCL4, PDGF-BB and IL9 were negatively related to anti-apoptotic PNH CD34+.

• In PNH, CD34+ cells express anti-apoptotic phenotype and high PI(3,4,5)P3 content.

• Cell-mediated immune attack in PNH is not corroborated by a skewed cytokine equilibrium.