Differences in gene expression and cytokine levels between newly diagnosed and chronic pediatric ITP

Jernås, Margareta; Hou, Yu; Célind, Frida Strömberg; Shao, Liming; Nookaew, Intawat; Wang, Qian; Ju, Xiuli; Mellgren, Karin; Wadenvik, Hans; Hou, Ming; Olsson, Bob

doi:10.1182/blood-2013-05-502807

Cited by 51 publications

(36 citation statements)

References 19 publications

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“…We recently reported higher expression levels of TNFRII on ITP Tregs, raising the possibility that impaired Treg compartment in ITP patients may be due to heightened sensitivity of ITP Tregs to TNF-α–mediated inhibition [25]. Indeed, higher levels of TNF-α are present in plasma/serum of ITP patients [26–28]. and we found that non-Treg CD4 + T cells from ITP patients expressed higher TNF-α levels.…”

Section: Role Of Inflammatory Cytokines In T-cell Dysregulation Inmentioning

confidence: 70%

Imbalanced immune homeostasis in immune thrombocytopenia

Yazdanbakhsh

2016

Seminars in Hematology

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Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders.

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Section: Role Of Inflammatory Cytokines In T-cell Dysregulation Inmentioning

confidence: 70%

Imbalanced immune homeostasis in immune thrombocytopenia

Yazdanbakhsh

2016

Seminars in Hematology

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“…Moreover, the etiology of ITP the disease remains unclear, with several different mechanisms demonstrated as precipitating causes91011). Analogously, the acute and chronic forms of ITP have demonstrated differences in pathophysiology1213). Collectively, these complex clinical and pathophysiologic features produce a markedly heterogeneous population of children with ITP, with associated diagnostic and therapeutic challenges.…”

Section: Discussionmentioning

confidence: 99%

Clinical course and prognostic factors of childhood immune thrombocytopenia: single center experience of 10 years

2016

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PurposeThis study aimed to evaluate the clinical course of childhood immune thrombocytopenia (ITP) and to assess the risk factors for developing chronic ITP.MethodsThe records of 64 children diagnosed with ITP from November 2005 and December 2014 at single center were retrospectively analyzed.ResultsThe median age at diagnosis and the median platelet count were 1 year (range, 1 month to 15 years) and 9×109/L (range, 0–84×109/L), respectively. No patient experienced severe bleeding. Nineteen children (29.7%) spontaneously recovered their platelet count to ≥100×109/L at a median of 10 days. In total 45 patients (70.3%) received intravenous immunoglobulin (IVIG) as first-line therapy, and showed platelet recovery at 1 week. The final diagnosis of 55 (85.9%) and 9 patients (14.1%) was acute and chronic ITP, respectively. Older age, absence of prior infection and insidious onset of symptoms were significantly associated with the development of chronic ITP. Among the patients who received IVIG, those with platelet count <45×109/L at 1 month after IVIG showed a significantly higher incidence of chronic ITP compared to those with platelet count ≥45×109/L (88.8% vs. 44.4%, P<0.01).ConclusionIn most patients, ITP runs a benign course and approximately 86% of them recover within 1 year of their initial diagnosis. The potential impact of the risk factors of chronic ITP on clinical practice needs to be explored and further studies are warranted to determine whether IVIG influences the course of ITP.

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“…In 2007, Dai et al [40] were the first to describe abnormal miRNA profiles in PBMCs of ITP patients, indicating that miRNA is involved in the pathogenesis of ITP. By applying genome-wide expression analyses of mRNA and miRNA, as well as the bioinformatic approach, investigators found that miRNA regulated several immunological pathways in T cells, further confirming an association of ITP development with microRNA dysfunction [41]. Recently, Li et al [42] found that interferon-γ, a cytokine known to promote the development of ITP [43,44], is a target of miR-409-3p, and decreased miR-409-3p in PBMCs is at least partially responsible for increased levels of interferon-γ.…”

Section: Discussionmentioning

confidence: 99%

Increased miR-155 Expression in Peripheral Blood Mononuclear Cells of Primary Immune Thrombocytopenia Patients Was Correlated with Serum Cytokine Profiles

Bian

Zhang³

et al. 2014

Acta Haematol

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We investigated the possiblepathogenic role of a microRNA (miR-155) in primary immune thrombocytopenia (ITP). We used quantitative real-time PCR to determine the relative expression of miR-155 and SOCS1 (suppressor of cytokine signaling) mRNA in peripheral blood mononuclear cells (PBMCs) from 28 ITP patients and 28 healthy controls. Cytokine plasma levels were determined by ELISA. Possible associations between miR-155 levels and serum cytokine concentrations were assessed using Spearman or Pearson correlation analysis. Seven naive ITP patients were followed and the effects of medical treatment on miR-155 levels were assessed. Compared to healthy controls, ITP patients had increased miR-155 and decreased SOCS1 mRNA levels. ITP patients also had increased plasma IL-17A and decreased IL-4, IL-10 and TGF-β₁ levels. miR-155 levels were negatively correlated with platelet counts, SOCS1 mRNA levels, and the plasma levels of IL-4, IL-10 and TGF-β₁, but positively correlated with plasma IL-17A levels. Medical treatment for ITP decreased miR-155 levels. Thus, our results suggest that miR-155 might be involved in the pathogenesis of ITP by regulating cytokine profiles, which may be mediated by miR-155 targeting SOCS1. © 2014 S. Karger AG, Basel

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Differences in gene expression and cytokine levels between newly diagnosed and chronic pediatric ITP

Abstract: Key Points Newly diagnosed and chronic ITP are most likely separate disease entities.

Cited by 51 publications

References 19 publications

Imbalanced immune homeostasis in immune thrombocytopenia

Imbalanced immune homeostasis in immune thrombocytopenia

Clinical course and prognostic factors of childhood immune thrombocytopenia: single center experience of 10 years

Increased miR-155 Expression in Peripheral Blood Mononuclear Cells of Primary Immune Thrombocytopenia Patients Was Correlated with Serum Cytokine Profiles

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