Immune thrombocytopenia: serum cytokine levels in children and adults

Abstract

BackgroundImmune thrombocytopenia (ITP) is an immune-mediated platelet disorder in which autoantibody-coated platelets are removed from the blood by monocytic phagocytes and there is impaired platelet production. There is a delicate balance of specific cytokine levels, which has an important role in the immune system and is known to be deregulated in autoimmune diseases. This study was designed to investigate the differences in Th cytokine levels between children and adults with newly diagnosed ITP and to compare these profiles to those found in healthy, age-matched controls.Material/MethodsThe concentration of IL-1α, IL-2, IL-3, IL-4, IL-6, IL-10, TNF-α, IFN-α, and IFN-γ in serum specimens was analyzed by enzyme-linked immunosorbent assay.ResultsAt the time of ITP diagnosis, children showed significantly lower serum levels of interleukin IL-2 and tumor necrosis factor TNF-α and higher serum level of IL-3 than healthy controls. Serum level of IL-4 in adult ITP patients was higher than those in control subjects. When compared with adults, children with ITP had lower serum level of IL-4, IL-6 and IFN-γ, and higher level of IFN-α.ConclusionsSignificant differences in serum cytokine levels between pediatric patients and healthy controls indicate that cytokine disturbances – especially changes in IL-2, IL-3 and TNF-α – might be involved in the pathogenesis of newly diagnosed ITP. TNF-α is the most informative variable for discrimination between healthy children and those with ITP.

In vitro TNF blockade enhances ex vivo expansion of regulatory T cells in patients with immune thrombocytopenia

“…Circulating TNF levels are elevated in ITP patients (Culic et al , 2013; Jernas et al , 2013; Talaat et al , 2014), but their levels in TNF expressing cells, such as CD4+ cells, has not been previously described in this patient population. We therefore measured TNF levels in CD4+ T cells from a group of patients with chronic ITP ( n = 23; median age 36, range 15–60 years; 15 males and 8 females with median platelet count 27 × 10 9 /l, range 8–466 × 10 9 /l; 14 were splenectomized), who had been without any ITP treatment for at least 2 weeks prior to the blood draw (Table I).…”

“…Treatment with TNF blockers has only been reported in a small group of patients with ITP, albeit efficacious in all 4 treated patients (McMinn et al , 2003; Litton, 2008). Higher levels of TNF have been reported in the plasma/serum from ITP patients,(Culic et al , 2013; Jernas et al , 2013; Talaat et al , 2014) although TNF expression levels in specific ITP cell types, such as CD4+ T lymphocytes, has not been examined. Interestingly, ITP patients have an increased frequency of TNF −308 A polymorphic allele associated with higher TNF-α production (Pehlivan et al , 2011; Sarpatwari et al , 2011; El Sissy et al , 2014).…”

“…TNFRSF1A is ubiquitously expressed on almost all cell types while TNFRSF1B is typically expressed on cells of the immune system including Tregs (Faustman & Davis, 2013). Surface expression of TNFRSF1B can be induced by IL1B, IL2 and TNF (Carpentier et al , 2004), cytokines reported to be increased in ITP patients (Rocha et al , 2010; Culic et al , 2013; Jernas et al , 2013; Talaat et al , 2014), although TNFRSF1B levels on Tregs in ITP patients have not been measured. It is generally accepted TNF can regulate Treg differentiation and proliferation, but the exact outcome appears to depend on Treg subset, the disease setting and the cytokine microenvironment (Biton et al , 2012).…”

CB2 Receptor Stimulation and Dexamethasone Restore the Anti-Inflammatory and Immune-Regulatory Properties of Mesenchymal Stromal Cells of Children with Immune Thrombocytopenia

“…Moreover, children with ITP have elevated levels of TNF-α [ 32 ]. For these reasons, we co-cultured MSCs from ITP patients with healthy PHA activated T-cells and analyzed lymphocytes viability and tumor necrosis factor-alpha (TNF-α) release after treatments.…”

Analysis of Interleukin-4 in Thrombocytopenia Autoimmune Patients

“…Cytokine balance regulates the immune system under normal and disturbed conditions in many autoimmune diseases. Several studies support the role of serum cytokines in the pathogenesis of ITP and provide evidence showing that polarized T-helper lymphocytes into Th1 and Th2 immune responses lead to B cell differentiation with the production of autoreactive antibodies in ITP (Pavelić, 2013. Differentiation of naïve T-helper cells into Th2 cells is stimulated by IL-4, which may be produced by mast cells, other tissue cells, and T cells themselves.…”