Increased levels of IL-10 and IL-1Ra counterbalance the proinflammatory cytokine pattern in acute pediatric immune thrombocytopenia. (June 2020)

• Record Type: Journal Article
• Authors: Goelz, Nadine; Bosch, Alessandra M.S.; Rand, Margaret L.; Eekels, Julia J.M.; Franzoso, Francesca D.; Schmugge, Markus
• Is Part Of: Cytokine. Volume 130(2020)
• Publication Date: 2020-06
• Subjects: ITP -- IVIg -- Cytokines -- Chemokines -- Autoimmune disease -- Growth factors -- Platelets; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2020.155078
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: Distinct cytokines patterns in pediatric ITP compared to controls. The pro- and anti-inflammatory activity in acute versus chronic ITP is counterbalanced. Positive correlation of ITP platelets counts with GRO and of monocytes with IP-10. Low PBMCs mRNA expression levels of cytokines in ITP compared to controls. Abstract: Immune thrombocytopenia (ITP) is an autoimmune disease which leads to accelerated platelet clearance. We investigated the plasma cytokine, chemokine and growth factor signatures and their clinical significance in pediatric ITP patients during acute, chronic and follow-up stages as well as the effects of intravenous immunoglobulin (IVIg) treatment, by using the Multiplex technology. In acute ITP before and/or after IVIg treatment we found significantly increased plasma levels of the pro- (tumour necrosis factor–α (TNF-α), interleukin IL-15) and anti- (IL-1 receptor antagonist (Ra), IL-10 and the growth factor interferon γ-induced protein (IP-10)) inflammatory cytokines, compared to healthy controls. Except for IL1-Ra, these cytokines decreased to normal levels in chronic patients. In contrast, growth-regulated α protein (GRO) and soluble CD40 ligand (sCD40L), known as platelet-derived molecules, were found to be significantly decreased in acute and increased in chronic ITP patients compared to healthy controls. GRO levels positively correlated with the platelet counts in the follow-up and chronic cohort. Monocyte counts showed a significant positive correlation only with IP-10 levels in acute ITP after IVIg treatment and follow-up patients. Expression levels of mRNAs for macrophage inflammatory protein MIP1-β, IL-1Ra and GRO determined in peripheral blood mononuclear cells (PBMCs) were significantly reduced in both acute and chronic ITP compared to controls. Our findings suggest that the different clinical presentation of acute and chronic pediatric ITP and to a lesser extent the IVIg treatment effects are characterized overall by a counterbalanced cytokine, chemokine and growth factor pattern response that might exert a pathogenic role in this disease.