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

Jernås, Margareta; Nookaew, Intawat; Wadenvik, Hans; Olsson, Bob

doi:10.1182/blood-2012-12-471250

Cited by 49 publications

(38 citation statements)

References 29 publications

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“…2,9 Real-time PCR was performed as previously described. 10 IL-4 and IL-16 were analyzed using commercial ELISAs from R&D systems (Minneapolis, MN).…”

Section: Methodsmentioning

confidence: 99%

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

Jernås

Hou

Célind

et al. 2013

Blood

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“…2,9 Real-time PCR was performed as previously described. 10 IL-4 and IL-16 were analyzed using commercial ELISAs from R&D systems (Minneapolis, MN).…”

Section: Methodsmentioning

confidence: 99%

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

Jernås

Hou

Célind

et al. 2013

Blood

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“…19 Hitherto, circumstantial evidence argues for a role for TFH in ITP, like changes of expression within circulating T cells of several microRNAs that target TFH markers such as CXCL13, IL-21, and Bcl6. 25 Moreover, plasma CXCL13 25 and IL-21 levels, 26 which are both produced by TFHs, are higher in active ITP patients compared with controls. Taken together with data from the murine model of AID showing the major role of TFHs during autoimmunity, we hypothesized that aberrant TFHs that recognized platelet antigens could participate in the proliferation and differentiation of autoreactive B cells recruited into GC, thus favoring antiplateletantibody production.…”

Section: Introductionmentioning

confidence: 99%

Splenic TFH expansion participates in B-cell differentiation and antiplatelet-antibody production during immune thrombocytopenia

Audia

Rossato

Santegoets

et al. 2014

Blood

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Key Points• Human splenic TFH expansion during ITP participates in B-cell differentiation and antiplateletantibody production.• IL-21 and CD40 are key TFH molecules that could be promising targets in the treatment of ITP.Antiplatelet-antibody-producing B cells play a key role in immune thrombocytopenia (ITP) pathogenesis; however, little is known about T-cell dysregulations that support B-cell differentiation. During the past decade, T follicular helper cells (TFHs) have been characterized as the main T-cell subset within secondary lymphoid organs that promotes B-cell differentiation leading to antibody class-switch recombination and secretion. Herein, we characterized TFHs within the spleen of 8 controls and 13 ITP patients. We show that human splenic TFHs are the main producers of interleukin (IL)-21, express CD40 ligand (CD154), and are located within the germinal center of secondary follicles. Compared with controls, splenic TFH frequency is higher in ITP patients and correlates with germinal center and plasma cell percentages that are also increased. In vitro, IL-21 stimulation combined with an anti-CD40 agonist antibody led to the differentiation of splenic B cells into plasma cells and to the secretion of antiplatelet antibodies in ITP patients. Overall, these results point out the involvement of TFH in ITP pathophysiology and the potential interest of IL-21 and CD40 as therapeutic targets in

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“…A significant increase in miR-155 expression [20] and decreased expression of miR-130a [21] and miR-409-3p [22] were previously reported for patients with ITP compared with normal controls. In addition, Jernas et al [23]. identified 17 miRNAs that regulate immunological pathways in T cells in ITP.…”

Section: Introductionmentioning

confidence: 99%

Differential Expression of MiR-106b-5p and MiR-200c-3p in Newly Diagnosed Versus Chronic Primary Immune Thrombocytopenia Patients Based on Systematic Analysis

Qian

Yan

et al. 2018

Cell Physiol Biochem

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Background/Aims: MicroRNAs (miRNAs) have been described to have important roles in primary immune thrombocytopenia (ITP). To gain additional understanding, we have now further evaluated the involvement of miRNAs in ITP. Methods: Microarray experiments were performed to examine the expression profiles of miRNAs and mRNAs in samples from subjects with newly diagnosed ITP (G1), chronic ITP (G2), and normal controls. The systematic Pipeline of Outlier MicroRNA Analysis framework was applied to identify key miRNAs expressed in the G1 and G2 samples. Quantitative PCR and receiver operator characteristic curves were used to confirm the performance of key miRNAs. Results: Compared with normal controls, 14 miRNAs (12 over-expressed and 2 under-expressed) and 7 over-expressed miRNAs were identified as key in G1 and G2 samples, respectively. miR-106b-5p, miR-200c-3p, and miR-92a-3p exhibited significantly different expression profiles among the groups. In particular, miR-106b-5p and miR-200c-3p were expressed at higher levels in patients with ITP compared to the normal controls. Furthermore, these two miRNAs expressions were even higher in patients with chronic ITP. Conclusion: MiR-106b-5p and miR-200c-3p may represent valuable biomarkers of ITP, although further studies are needed to confirm and assess the value of these potential biomarkers at various stages of ITP.

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

Abstract: Key Points MicroRNA and plasma levels of the target gene CXCL13 differ between ITP and controls indicating that microRNA may be important in ITP.

Cited by 49 publications

References 29 publications

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

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

Splenic TFH expansion participates in B-cell differentiation and antiplatelet-antibody production during immune thrombocytopenia

Differential Expression of MiR-106b-5p and MiR-200c-3p in Newly Diagnosed Versus Chronic Primary Immune Thrombocytopenia Patients Based on Systematic Analysis

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