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MicroRNA regulate immunological pathways in T-cells in immune thrombocytopenia (ITP).

ABSTRACT: MicroRNA are small noncoding RNA molecules that regulate gene expression. To investigate the role of microRNA in immune thrombocytopenia (ITP), we performed genome-wide expression analyses of mRNA and microRNA in T cells from ITP patients and controls. We identified 1915 regulated genes and 22 regulated microRNA that differed between ITP patients and controls. Seventeen of the 22 regulated microRNA were linked to changes in target gene expression; 57 of these target genes were associated with the immune system, eg, T-cell activation and regulation of immunoglobulin production. CXCL13 and IL-21 were two microRNA target genes significantly increased in ITP. We could demonstrate increased plasma levels of CXCL13 and others have reported increased plasma levels of interleukin-21 in ITP. Thus, regulated microRNA were significantly associated with both gene and protein expression of molecules in immunological pathways. We suggest that microRNA may be important regulatory molecules involved in the loss of tolerance in ITP.

SUBMITTER: Jernas M

PROVIDER: S-EPMC3596969 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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MicroRNA regulate immunological pathways in T-cells in immune thrombocytopenia (ITP).

Jernås Margareta M Nookaew Intawat I Wadenvik Hans H Olsson Bob B

Blood 20130109 11

MicroRNA are small noncoding RNA molecules that regulate gene expression. To investigate the role of microRNA in immune thrombocytopenia (ITP), we performed genome-wide expression analyses of mRNA and microRNA in T cells from ITP patients and controls. We identified 1915 regulated genes and 22 regulated microRNA that differed between ITP patients and controls. Seventeen of the 22 regulated microRNA were linked to changes in target gene expression; 57 of these target genes were associated with th ...[more]

PMID: 23303824

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Project description:Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by isolated thrombocytopenia caused by increased platelet destruction and impaired platelet production. First-line therapies include corticosteroids, intravenous immunoglobulin, and anti-D immunoglobulin. For patients who are refractory to these therapies, those who become corticosteroid dependent, or relapse following treatment with corticosteroid, options include splenectomy, rituximab, and thrombopoietin-receptor agonists, alongside a variety of additional immunosuppressive and experimental therapies. Despite recent advances in the management of ITP, many areas need further research. Although it is recognized that an assessment of patient-reported outcomes in ITP is valuable to understand and guide treatment, these measures are not routinely measured in the clinical setting. Consequently, although corticosteroids are first-line therapies for both children and adults, there are no data to suggest that corticosteroids improve health-related quality of life or other patient-related outcomes in either children or adults. In fact, long courses of corticosteroids, in either children or adults, may have a negative impact on a patient's health-related quality of life, secondary to the impact on sleep disturbance, weight gain, and mental health. In adults, additional therapies may be needed to treat overt hemorrhage, but unfortunately the results are transient for the majority of patients. Therefore, there is a need to recognize the limitations of current existing therapies and evaluate new approaches, such as individualized treatment based on the probability of response and the size of effect on the patient's most bothersome symptoms and risk of adverse effects or complications. Finally, a validated screening tool that identifies clinically significant patient-reported outcomes in routine clinical practice would help both patients and physicians to effectively follow a patient's health beyond simply treating the laboratory findings and physical symptoms of ITP. The goal of this narrative review is to discuss management of newly diagnosed and refractory patients with ITP, with a focus on the limitations of current therapies from the patient's perspective.

Dataset Information

MicroRNA regulate immunological pathways in T-cells in immune thrombocytopenia (ITP).

Publications

MicroRNA regulate immunological pathways in T-cells in immune thrombocytopenia (ITP).

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