CD4+CD39 T CELLS IN THE PERIPHERAL BLOOD AND SPLEEN OF PATIENTS WITH IMMUNE THROMBOCYTOPENIA

CD4+CD39 T CELLS IN THE PERIPHERAL BLOOD AND SPLEEN OF PATIENTS WITH IMMUNE THROMBOCYTOPENIA

Authors

  • SOPHIO METREVELI
  • NINO NANAVA
  • IRINE KVACHADZE
  • TINATIN CHIKOVANI
  • NONA JANIKASHVILI

DOI:

https://doi.org/10.52340/jecm.2022.06.05.09

Keywords:

Primary immune thrombocytopenia, CD4 CD39 T cells, blood, spleen

Abstract

Primary immune thrombocytopenia (ITP) is characterized with decreased platelet count and increased risk of bleeding. The mechanism of thrombocytopenia in ITP is incompletely understood but thought to involve autoantibodies which are produced by the B cells and are stimulated by helper T cells. Regulatory T cells (Treg) have been seen to be significant in ITP pathogenesis. Recent studies have reported reduction of circulating Treg cells in ITP patients but similar levels with controls have also been observed. The ectoenzyme CD39 is highly expressed on the surface of Treg cells and can suggest its immunosuppressive function.In this study we aimed to analyze CD4+CD39+ T lymphocytes both in the blood and spleen of patients with ITP who did not respond to the first line treatment and underwent splenectomy as a second line therapy. Non-ITP patients undergoing splenectomy were involved in the control group. Our data demonstrates significant diminution of in splenic but not circulating CD4+CD39+ T cells in ITP patients compared to controls. Of note, the comparison of spleen and peripheral CD4+CD39+T lymphocytes indicates that the frequency of CD39+ Treg cells is more stable in spleen compared to blood in ITP patients. Our data suggests the potential of CD39 as an important biomarker for ITP and underlines the clinical and scientific value of spleen immune analyzes in this pathology.

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References

R. Article, “Receptors That Are Expressed By Tissue Macrophages, Predominantly in the Spleen,” English J., vol. 346, no. 13, pp. 995–1008, 2011.

D. Nugent, R. McMillan, J. L. Nichol, and S. J. Slichter, “Pathogenesis of chronic immune thrombocytopenia: Increased platelet destruction and/or decreased platelet production,” Br. J. Haematol., vol. 146, no. 6, pp. 585–596, 2009, doi: 10.1111/j.1365-2141.2009.07717.x.

H. Frederiksen and K. Schmidt, “The incidence of idiopathic thrombocytopenic purpura in adults increases with age,” Blood, vol. 94, no. 3, pp. 909–913, 1999, doi: 10.1182/blood.v94.3.909.415k02_909_913.

J. B. Segal and N. R. Powe, “Prevalence of immune thrombocytopenia: Analyses of administrative data,” J. Thromb. Haemost., vol. 4, no. 11, pp. 2377–2383, 2006, doi: 10.1111/j.1538-7836.2006.02147.x.

G. Moulis, A. Palmaro, J. L. Montastruc, B. Godeau, M. Lapeyre-Mestre, and L. Sailler, “Epidemiology of incident immune thrombocytopenia: A nationwide population-based study in France,” Blood, vol. 124, no. 22, pp. 3308–3315, 2014, doi: 10.1182/blood-2014-05-578336.

M. Kuwana, J. Kaburaki, and Y. Ikeda, “Autoreactive T cells to platelet GPIIb-IIIa in immune thrombocytopenic purpura: Role in production of anti-platelet autoantibody,” J. Clin. Invest., vol. 102, no. 7, pp. 1393–1402, 1998, doi: 10.1172/JCI4238.

M. Kuwana, Y. Okazaki, J. Kaburaki, Y. Kawakami, and Y. Ikeda, “Spleen Is a Primary Site for Activation of Platelet-Reactive T and B Cells in Patients with Immune Thrombocytopenic Purpura,” J. Immunol., vol. 168, no. 7, pp. 3675–3682, 2002, doi: 10.4049/jimmunol.168.7.3675.

S. Audia et al., “Splenic TFH expansion participates in B-cell differentiation and antiplatelet-antibody production during immune thrombocytopenia,” Blood, vol. 124, no. 18, pp. 2858–2866, 2014, doi: 10.1182/blood-2014-03-563445.

S. Audia et al., “B cell depleting therapy regulates splenic and circulating T follicular helper cells in immune thrombocytopenia,” J. Autoimmun., vol. 77, pp. 89–95, 2017, doi: 10.1016/j.jaut.2016.11.002.

B. Olsson, P. Andersson, M. Jernås, S. Jacobsson, and B. Carlsson, “T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura,” no. Cdc, p. 12937414, 2003, doi: 10.1038/nm921.

B. Olsson, M. Jernås, and H. Wadenvik, “Increased plasma levels of granzymes in adult patients with chronic immune thrombocytopenia,” no. Cdc, p. 22476618, 2012, doi: 10.1160/TH12-01-0012.

S. Audia et al., “Preferential splenic CD8+ T-cell activation in rituximab-nonresponder patients with immune thrombocytopenia,” Blood, vol. 122, no. 14, pp. 2477–2486, 2013

L. J. Toltl and D. M. Arnold, “Pathophysiology and management of chronic immune thrombocytopenia: Focusing on what matters,” Br. J. Haematol., vol. 152, no. 1, pp. 52–60, 2011, doi: 10.1111/j.1365-2141.2010.08412.x.

M. Kuwana, J. Kaburaki, Y. Okazaki, H. Miyazaki, and Y. Ikeda, “Two types of autoantibody-mediated thrombocytopenia in patients with systemic lupus erythematosus,” Rheumatology, vol. 45, no. 7, pp. 851–854, 2006, doi: 10.1093/rheumatology/kel010.

M. Michel et al., “Platelet autoantibodies and lupus-associated thrombocytopenia,” Br. J. Haematol., vol. 119, no. 2, pp. 354–358, 2002, doi: 10.1046/j.1365-2141.2002.03817.x.

M. Sakakura et al., “Reduced Cd4+Cd25+ T cells in patients with idiopathic thrombocytopenic purpura,” Thromb. Res., vol. 120, no. 2, pp. 187–193, 2007, doi: 10.1016/j.thromres.2006.09.008.

Y. Ling, X. Cao, Z. Yu, and C. Ruan, “Circulating dendritic cells subsets and CD4+Foxp3+ regulatory T cells in adult patients with chronic ITP before and after treatment with high-dose dexamethasome,” Eur. J. Haematol., vol. 79, no. 4, pp. 310–316, 2007, doi: 10.1111/j.1600-0609.2007.00917.x.

B. Liu et al., “Abnormality of CD4+CD25+ regulatory T cells in idiopathic thrombocytopenic purpura,” Eur. J. Haematol., vol. 78, no. 2, pp. 139–143, 2007, doi: 10.1111/j.1600-0609.2006.00780.x.

J. Yu et al., “Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura,” Blood, vol. 112, no. 4, pp. 1325–1328, 2008

S. Audia et al., “Immunologic effects of rituximab on the human spleen in immune thrombocytopenia,” Blood, vol. 118, no. 16, pp. 4394–4400, 2011, doi: 10.1182/blood-2011-03-344051.

K. M. Dwyer et al., “Expression of CD39 by human peripheral blood CD4+CD25 + T cells denotes a regulatory memory phenotype,” Am. J. Transplant., vol. 10, no. 11, pp. 2410–2420, 2010, doi: 10.1111/j.1600-6143.2010.03291.x.

Y. Lu et al., “The abnormal function of CD39+ regulatory T cells could be corrected by high-dose dexamethasone in patients with primary immune thrombocytopenia,” Ann. Hematol., vol. 98, no. 8, pp. 1845–1854, 2019, doi: 10.1007/s00277-019-03716-9.

F. Rodeghiero, “A critical appraisal of the evidence for the role of splenectomy in adults and children with ITP,” Br. J. Haematol., vol. 181, no. 2, pp. 183–195, 2018, doi: 10.1111/bjh.15090.

W. Ghanima, B. Godeau, D. B. Cines, and J. B. Bussel, “How I treat immune thrombocytopenia: The choice between splenectomy or a medical therapy as a second-line treatment,” Blood, vol. 120, no. 5, pp. 960–969, 2012, doi: 10.1182/blood-2011-12-309153.

B. J. N. George et al., “Idiopathic Thrombocytopenic Purpura:,” vol. 88, no. 1, pp. 3–40, 1996.

D. B. Cines and J. B. Bussel, “How I treat idiopathic thrombocytopenic purpura (ITP),” Blood, vol. 106, no. 7, pp. 2244–2251, 2005, doi: 10.1182/blood-2004-12-4598.

K. Kojouri, S. K. Vesely, D. R. Terrell, and J. N. George, “Splenectomy for adult patients with idiopathic thrombocytopenic purpura: A systematic review to assess long-term platelet count responses, prediction of response, and surgical complications,” Blood, vol. 104, no. 9, pp. 2623–2634, 2004, doi: 10.1182/blood-2004-03-1168.

P. Fenaux, M. T. Caulier, M. C. Hirschauer, R. Beuscart, J. Goudemand, and F. Bauters, “Reevaluation of the prognostic factors for splenectomy in chronic idiopathic thrombocytopenic purpura (ITP): A report on 181 cases,” Eur. J. Haematol., vol. 42, no. 3, pp. 259–264, 1989, doi: 10.1111/j.1600-0609.1989.tb00109.x.

B. Allard, M. S. Longhi, S. C. Robson, and J. Stagg, “The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets,” Immunol. Rev., vol. 276, no. 1, pp. 121–144, 2017, doi: 10.1111/imr.12528.

B. N. Cronstein, “Low-dose methotrexate: A mainstay in the treatment of rheumatoid arthritis,” Pharmacol. Rev., vol. 57, no. 2, pp. 163–172, 2005, doi: 10.1124/pr.57.2.3.

R. S. Peres et al., “Low expression of CD39 on regulatory T cells as a biomarker for resistance to methotrexate therapy in rheumatoid arthritis,” Proc. Natl. Acad. Sci. U. S. A., vol. 112, no. 8, pp. 2509–2514, 2015, doi: 10.1073/pnas.1424792112.

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Published

2022-06-06

How to Cite

SOPHIO METREVELI, NINO NANAVA, IRINE KVACHADZE, TINATIN CHIKOVANI, & NONA JANIKASHVILI. (2022). CD4+CD39 T CELLS IN THE PERIPHERAL BLOOD AND SPLEEN OF PATIENTS WITH IMMUNE THROMBOCYTOPENIA. Experimental and Clinical Medicine Georgia, (5). https://doi.org/10.52340/jecm.2022.06.05.09

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