T-cell Imbalance or Decreased Th:Tc Ratio in Immune Thrombocytopenia: Is it Clinically Significant?

Aisha Arshad, Samina Naz Mukry, Munira Borhany, Tahir Shamsi

Abstract


Background: 

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by low platelet count and various contributing factors. The imbalance in T cells may also cause ITP. Therefore, the present study was planned to assess the role of T-cells in the pathogenesis of ITP and to evaluate any possible link of Th: Tc imbalance to disease severity.

Methods: The present study was conducted with 111 patients of ITP and similar number of controls as case-control study with a 1:1 ratio of from January 2017 to July 2019. The patients were grouped according to the guidelines of ASH as newly diagnosed/persistent ITP(ND-ITP/P-ITP) and chronic/refractory ITP(C-ITP/R-ITP). The blood samples were obtained, and CBC parameters were observed using advanced hematology analyzer XN-1000. The T cell subset analysis was evaluated by BD FACSCalibur flow cytometer. The Fisher’s exact test was done to evaluate the difference among the groups with (p < 0.05) by using SPSS version 19.

Results: Significantly reduced levels of hemoglobin and platelet counts, with elevated IPF were observed in ND-ITP/P-ITP and C-ITP/R-ITP patients (p=<0.001).The significantly low Th:Tc ratio (p=<0.001) predicts imbalance of T cells in ND-ITP/P-ITP (0.86±0.47) as compared to control group (1.73±0.46).The mean of 0.84±0.34 Th:Tc ratio was observed in C-ITP/R-ITP children ≤16 years. No significant difference (P = 0.89) was found among children with non-severe chronic (0.84±0.42), severe chronic (0.82±0.49), and refractory ITP (0.85±0.51).

Conclusion: In ITP patients’ low levels of Th:Tc ratio was observed suggesting dysregulation of immune system. The chronicity of the disease may be linked to elevated production of Tc in children (≤16 years) with C-ITP/R-ITP.

Keywords: Immune thrombocytopenia; Platelets counts; Helper T-cells (Th); Cytotoxic T-cells (Tc)

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References


Coopamah MD, Garvey MB, Freedman J, Semple JW. Cellular immune mechanisms in autoimmune thrombocytopenic purpura: An update. Transfusion Medicine Reviews, (2003); 17(1): 69-80.

Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med, (2002); 346(13): 995-1008.

Stasi R, Evangelista ML, Stipa E, Buccisano F, Venditti A, Amadori S. Idiopathic thrombocytopenic purpura: current concepts in pathophysiology and management. Thrombosis and Haemostasis, (2008); 99(01): 4-13.

Nomura S. Advances in diagnosis and treatments for immune thrombocytopenia. Clinical Medicine Insights: Blood Disorders, (2016); 9: 15-22.

Zhang F, Chu X, Wang L, Zhu Y, Li L, Ma D, Peng J, Hou M. Cell‐mediated lysis of autologous platelets in chronic idiopathic thrombocytopenic purpura. European Journal of Haematology, (2006); 76(5): 427-431.

Cines DB, Bussel JB, Liebman HA, Luning Prak ET. The ITP syndrome: pathogenic and clinical diversity. Blood, The Journal of the American Society of Hematology, (2009); 113(26): 6511-6521.

Ogawara H, Handa H, Morita K, Hayakawa M, Kojima J, Amagai H, Tsumita Y, Kaneko Y, Tsukamoto N, Nojima Y, Murakami H. High Th1/Th2 ratio in patients with chronic idiopathic thrombocytopenic purpura. European Journal of Haematology, (2003); 71(4): 283-288.

Kuwana M, Kaburaki J, Kitasato H, Kato M, Kawai S, Kawakami Y, Ikeda Y. Immunodominant epitopes on glycoprotein IIb-IIIa recognized by autoreactive T cells in patients with immune thrombocytopenic purpura. Blood, The Journal of the American Society of Hematology, (2001); 98(1): 130-139.

Culic S, Labar B, Marusic A, Salamunic I. Correlations among age, cytokines, lymphocyte subtypes, and platelet counts in autoimmune thrombocytopenic purpura. Pediatric Blood and Cancer, (2006); 47(5): 671-674.

Talaat RM, Elmaghraby AM, Barakat SS, El-Shahat M. Alterations in immune cell subsets and their cytokine secretion profile in childhood idiopathic thrombocytopenic purpura (ITP). Clin Exp Immunol, (2014): 176(2): 291-300.

Neunert C, Lim W, Crowther M, Cohen A, Solberg Jr L, Crowther MA. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood, The Journal of the American Society of Hematology, (2011); 117(16): 4190-4207.

Cines DB, Bussel JB. How I treat idiopathic thrombocytopenic purpura (ITP). Blood. The Journal of the American Society of Hematology, (2005); 106(7): 2244-2251.

Stasi R, Stipa E, Masi M, Cecconi M, Scimò MT, Oliva F, Sciarra A, Perrotti AP, Adomo G, Amadori S, Papa G. Long-term observation of 208 adults with chronic idiopathic thrombocytopenic purpura. The American journal of medicine, (1995); 98(5): 436-442.

Page LK, Psaila B, Provan D, Michael Hamilton J, Jenkins JM, Elish AS, Lesser ML, Bussel JB. The immune thrombocytopenic purpura (ITP) bleeding score: assessment of bleeding in patients with ITP.The British Journal of Haematology, (2007); 138(2): 245-248.

Naz A, Mukry SN, Shaikh MR, Bukhari AR, Shamsi TS. Importance of immature platelet fraction as predictor of immune thrombocytopenic purpura. Pakistan Journal of Medical Sciences, (2016); 32(3): 575-579.

Briggs C, Kunka S, Hart D, Oguni S, Machin SJ. Assessment of an immature platelet fraction (IPF) in peripheral thrombocytopenia. British Journal of Haematology, (2004); 126(1): 93-99.

Zhao C, Li X, Zhang F, Wang L, Peng J, Hou M. Increased cytotoxic T-lymphocyte-mediated cytotoxicity predominant in patients with idiopathic thrombocytopenic purpura without platelet autoantibodies.Haematologica, (2008); 93(9): 1428-1430.

Yang L, Wang L, Zhao CH, Zhu XJ, Hou Y, Jun P, Hou M. Contributions of TRAIL-mediated megakaryocyte apoptosis to impaired megakaryocyte and platelet production in immune thrombocytopenia. Blood,The Journal of the American Society of Hematology, (2010); 116(20): 4307-4316.

Semple JW, Milev Y, Cosgrave D, Mody M, Hornstein A, Blanchette V, Freedman J. Differences in serum cytokine levels in acute and chronic autoimmune thrombocytopenic purpura: relationship to platelet phenotype and antiplatelet T-cell reactivity. Blood, The American Journal of Hematology, (1996); 87(10): 4245-4254.

Sakakura M, Wada H, Tawara I, Nobori T, Sugiyama T, Sagawa N, Shiku H. Reduced Cd4+ Cd25+ T cells in patients with idiopathic thrombocytopenic purpura. Thrombosis Research, (2007); 120(2): 187-193.

Olsson B, Andersson PO, Jernås M, Jacobsson S, Carlsson B, Carlsson LM, Wadenvik H. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med, (2003); 9(9): 1123-1124.

Zhao Z, Yang L, Yang G, Zhuang Y, Qian X, Zhou X, Xiao D, Shen Y. Contributions of T lymphocyte abnormalities to therapeutic outcomes in newly diagnosed patients with immune thrombocytopenia. PLoS One, (2015); 10(5): e0126601.

Zahran AM, Elsayh KI. CD4+ CD25+ High Foxp3+ regulatory T cells, B lymphocytes, and T lymphocytes in patients with acute ITP in Assiut Children Hospital. Clin Appl Thromb Hemost, (2014); 20(1): 61-67.

Sala P, Tonutti E, Feruglio C, Florian F, Colombatti A. Persistent expansions of CD4+ CD8+ peripheral blood T cells. Blood. The American Journal of Hematology, (1993); 82(5): 1546-1552.

Hirao JI, Sugita K. Circulating CD4+ CD8+ T lymphocytes in patients with Kawasaki disease. Clinical and Experimental Immunology, (1998); 111(2): 397-401.

Berrih S, Gaud C, Bach MA, Le Brigand H, Binet JP, Bach JF. Evaluation of T cell subsets in myasthenia gravis using anti-T cell monoclonal antibodies. Clinical and Experimental Immunology, (1981); 45(1): 1-8.

Waschbisch A, Sammet L, Schröder S, Lee DH, Barrantes-Freer A, Stadelmann C, Linker RA. Analysis of CD4+ CD8+ double-positive T cells in blood, cerebrospinal fluid and multiple sclerosis lesions. Clinical and Experimental Immunology, (2014); 177(2): 404-411.

Scott CS, Wheeler R, Ford P, Bynoe AG, Roberts BE. T lymphocyte subpopulations in idiopathic thrombocytopenic purpura (ITP). Scandinavian Journal of Haematology, (1983); 30(5): 401-406.

El-Rashedi FH, El-Hawy MA, Helwa MA, Abd-Allah SS. Study of CD4+, CD8+, and natural killer cells (CD16+, CD56+) in children with immune thrombocytopenic purpura. Hematology/oncology and Stem Cell Therapy, (2017); 10(1): 8-14.




DOI: http://dx.doi.org/10.62940/als.v10i1.1654

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