New aspects in pathogenesis in Patients with Immune Thrombocytopenia

Document Type : Original Article

Authors

1 Clinical and Chemical Pathology Department, Faculty of Medicine, Beni-Suef University

2 Pediatric Medicine Department, Faculty of Medicine, Beni-Suef University

3 Clinical and chemical pathology , faculty of medicine , Beni suef university, Beni suef , Egypt

Abstract

Background: Immune thrombocytopenia is an auto immune disorder characterized by low platelet count due to either peripheral platelet destruction or inappropriate production of platelets by bone marrow. although auto antibodies have been showed as the principle factor in the pathogenesis of ITP, also cellular immune modulation have been identified to have a very important role in the pathophysiology of ITP. the aim of this study was to investigate runt related transcription factor 1 (Runx1) and it`s association to ITP. Aim of the Work: To determine the expression levels of runt related transcription factor in the peripheral blood of children with ITP and to determine the clinical usefulness of this transcription factor in understanding the pathophysiology of ITP and its relation to disease activity and chronicity. Patients and Methods: This study was conducted on 49 patients having ITP in beni-suef university hospital and 20 healthy subjects as controls. RUNX1 was analyzed using ELISA technique. Results: The results revealed that RUNX-1 levels were significantly higher in ITP patients compared to controls (1.78 ±0.73 vs. 3.87 ±2.39, p=0.001) in healthy controls and ITP patients respectively. Conclusion: RUNX1 is involved in the pathogenesis of ITP, it also related to disease activity

Keywords

Main Subjects


  1. Cooper, N., & Ghanima, W. (2019). Immune thrombocytopenia. New England Journal of Medicine, 381(10), 945-955.‏
  2. Kohli, R., & Chaturvedi, S. (2019). Epidemiology and clinical manifestations of immune thrombocytopenia. Hämostaseologie, 39(03), 238-249.
  3. Lo, E., & Deane, S. (2014). Diagnosis and classification of immune-mediated thrombocytopenia. Autoimmunity reviews, 13(4-5), 577-583.‏
  4. Wen, R., Wang, Y., Hong, Y., & Yang, Z. (2020). Cellular immune dysregulation in the pathogenesis of immune thrombocytopenia. Blood Coagulation & Fibrinolysis, 31(2), 113-120.‏
  5. Li, Q., Liu, Y., Wang, X., Sun, M., Wang, L., Wang, X., & Guo, X. (2021). Regulation of Th1/Th2 and Th17/Treg by pDC/mDC imbalance in primary immune thrombocytopenia. Experimental Biology and Medicine, 159-168.‏
  6. Zhang, D., Liang, C., Li, P., Yang, L., Hao, Z., Kong, L., & Du, B. (2021). Runt‐related transcription factor 1 (Runx1) aggravates pathological cardiac hypertrophy by promoting p53 expression. Journal of cellular and molecular medicine, 25(16), 7867-7877.‏
  7. Songdej, N., & Rao, A. K. (2019). Inherited platelet defects and mutations in hematopoietic transcription factor RUNX1. Hematopathology, 317-325.‏
  8. Neunert, C., Terrell, D. R., Arnold, D. M., Buchanan, G., Cines, D. B., Cooper, N., & Vesely, S. K. (2019). American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood advances, 3(23), 3829-3866.‏
  9. Green, S. J., Venkatramanan, R., & Naqib, A. (2015). Deconstructing the polymerase chain reaction: understanding and correcting bias associated with primer degeneracies and primer-template mismatches. PloS one, 10(5), e0128122.‏
  10. Dorak, M. T. (Ed.). (2007). Real-time PCR. Taylor & Francis.‏
  11. Rahman, M. T., Uddin, M. S., Sultana, R., Moue, A., & Setu, M. (2013). Polymerase chain reaction (PCR): a short review. Anwer Khan Modern Medical College Journal, 4(1), 30-36.‏
  12. Green, M. R., & Sambrook, J. (2018). Analysis and normalization of real-time polymerase chain reaction (PCR) experimental data. Cold Spring Harbor Protocols, 10.‏
  13. Ma, L., Zeng, F., Cong, F., Huang, B., Huang, R., Ma, J., & Guo, P. (2019). Development of a SYBR green-based real-time RT-PCR assay for rapid detection of the emerging swine acute diarrhea syndrome coronavirus. Journal of virological methods, 265, 66–70.
  14. Malkamäki, S., Näreaho, A., Lavikainen, A., Oksanen, A., & Sukura, A. (2019). A new SYBR green real-time PCR assay for semi-quantitative detection of Echinococcus multilocularis and Echinococcus canadensis DNA on bilberries (Vaccinium myrtillus). Food and waterborne parasitology, 17, e00068.‏
  15. Smith, C. J., & Osborn, A. M. (2009). Advantages and limitations of quantitative PCR (Q-PCR)-based approaches in microbial ecology. FEMS microbiology ecology, 67(1), 6-20.‏
  16. Maouia, A., Rebetz, J., Kapur, R., & Semple, J. W. (2020). The immune nature of platelets revisited. Transfusion Medicine Reviews; 145-167.
  17. Alcedo, P., Andrade, E., Hamad, H., & Rivero, G. (2017). Cytogenetic, Inflammatory, Immunologic, and Infectious Basis for Dysplastic Hematopoeisis. Oncol Hematol Rev, 13, 81-91.
  18. Collins, A., Littman, D. R., & Taniuchi, I. (2009). RUNX proteins in transcription factor networks that regulate T-cell lineage choice. Nature Reviews Immunology, 9(2), 106-115.
  19. Shin, B., Hosokawa, H., Romero-Wolf, M., Zhou, W., Masuhara, K., Tobin, V. R., & Rothenberg, E. V. (2021). Runx1 and Runx3 drive progenitor to T-lineage transcriptome conversion in mouse T cell commitment via dynamic genomic site switching. Proceedings of the National Academy of Sciences, 118(4).
  20. Zhang, F., Meng, G., & Strober, W. (2008). Interactions among the transcription factors Runx1, RORγt and Foxp3 regulate the differentiation of interleukin 17–producing T cells. Nature immunology, 9(11), 1297-1306.‏
  21. Lazarevic, V., Chen, X., Shim, J. H., Hwang, E. S., Jang, E., Bolm, A. N., & Glimcher, L. H. (2011). T-bet represses TH17 differentiation by preventing Runx1-mediated activation of the gene encoding RORγt. Nature immunology, 12(1), 96-104.‏
  22. Liu, H. P., Cao, A. T., Feng, T., Li, Q., Zhang, W., Yao, S., & Cong, Y. (2015). TGF‐β converts Th1 cells into Th17 cells through stimulation of Runx1 expression. European journal of immunology, 45(4), 1010-1018.‏
  23. Otálora, B. A., Henríquez, B., López Kleine, L., & Rojas, A. (2019). RUNX family: Oncogenes or tumor suppressors. Oncology reports, 42(1), 3-19
  24. Bevington, S. L., Keane, P., Soley, J. K., Tauch, S., Gajdasik, D. W., Fiancette, R., & Cockerill, P. N. (2020). IL‐2/IL‐7‐inducible factors pioneer the path to T cell differentiation in advance of lineage‐defining factors. The EMBO journal, 39(22), e105220.
  25. Ono, M. (2020). Control of regulatory T‐cell differentiation and function by T‐cell receptor signalling and Foxp3 transcription factor complexes. Immunology, 160(1), 24-37.
  26. Wang, Q., Li, J., Yu, T. S., Liu, Y., Li, K., Liu, S., & Liu, X. G. (2019). Disrupted balance of CD4+ T-cell subsets in bone marrow of patients with primary immune thrombocytopenia. International journal of biological sciences, 15(13), 2798.
  27. Kostic, M., Zivkovic, N., Cvetanovic, A., & Marjanović, G. (2020). CD4+ T cell phenotypes in the pathogenesis of immune thrombocytopenia. Cellular immunology, 351, 104096.
  28. Bahoush, G., Ghasemi, S., Mohsen Razavi, S., Faranoush, M., & Nojoomi, M. (2019). Predictive Value of Risk Factors for Chronic Idiopathic Thrombocytopenic Purpura in Patients with Acute Type of Disease. Available at SSRN 3448026
  29. Schmidt, D. E., Wendtland Edslev, P., Heitink‐Pollé, K. M., Mertens, B., Bruin, M. C., Kapur, R., & de Haas, M. (2021). A clinical prediction score for transient versus persistent childhood immune thrombocytopenia. Journal of Thrombosis and Haemostasis, 19(1), 121-130.
  30. Wong, M. S. C., Chan, G. C. F., Ha, S. Y., & Lau, Y. L. (2012). Clinical characteristics of chronic idiopathic thrombocytopenia in Chinese children. Journal of pediatric hematology/oncology, 24(8), 648-652.
  31. Zhong, X., Wu, Y., Liu, Y., Zhu, F., Li, X., Li, D., & Xu, K. (2016). Increased RUNX1 expression in patients with immune thrombocytopenia. Human immunology, 77(8), 687-691.‏
  32. Bal, G., Futschik, M. E., Hartl, D., Ringel, F., Kamhieh‐Milz, J., Sterzer, V., & Salama, A. (2016). Identification of novel biomarkers in chronic immune thrombocytopenia (ITP) by microarray‐based serum protein profiling. British journal of haematology, 172(4), 602-615.‏
  33. Perez Botero, J., Chen, D., Cousin, M. A., Majerus, J. A., Coon, L. M., Kruisselbrink, T. M., & Patnaik, M. M. (2017). Clinical characteristics and platelet phenotype in a family with RUNX1 mutated thrombocytopenia. Leukemia & Lymphoma, 58(8), 1963-1967.‏
  34. Elnaenaey, W. A., Omar, O. M., & Aboelwafa, R. A. (2021). Increased Expression of IL-17A and IL-17F Is Correlated With RUNX1 and RORγT in Pediatric Patients With Primary Immune Thrombocytopenia. Journal of Pediatric Hematology/Oncology, 43(3), e320-e327.‏