INTERLEUKIN-21 IN PATIENTS WITH IMMUNE THROMBOCYTOPENIA WHO UNDERWENT SPLENECTOMY

SOPHIO METREVELI; IRINE KVACHADZE; NINO KIKODZE; NINO NANAVA; TINATIN CHIKOVANI; NONA JANIKASHVILI

doi:10.52340/jecm.2022.03.15

INTERLEUKIN-21 IN PATIENTS WITH IMMUNE THROMBOCYTOPENIA WHO UNDERWENT SPLENECTOMY

Authors

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

DOI:

https://doi.org/10.52340/jecm.2022.03.15

Abstract

Antiplatelet autoantibodies that are produced as a result of B and T lymphocyte interactions are regarded to have a cardinal role in the pathogenesis of immune thrombocytopenia (ITP). In numerous autoimmune disorders, interleukin-21 (IL-21) is suggested to play an important role in the B cell stimulation by follicular helper T (TFH) and the enhancement of autoantibody production. The present study aimed to explore the levels of IL-21 in ITP patients who did not respond to first line treatment and had splenectomy as a second line therapy. Control group was comprised by patients who underwent splenectomy for other reasons than autoimmune or malignant hematological pathologies. Our results showed no significant difference in plasma levels of IL-21 between ITP patients and controls. Nevertheless, our data have clinically and scientifically important value, further investigations, considering previous treatments, refined controls and other research limitations, are needed to understand the detailed role of IL-21 in ITP pathogenesis.

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References

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.

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. 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.

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.

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.

V. L. Patel, J. Schwartz, and J. B. Bussel, “The effect of anti-CD40 ligand in immune thrombocytopenic purpura,” Br. J. Haematol., vol. 141, no. 4, pp. 545–548, 2008, doi: 10.1111/j.1365-2141.2008.07039.x.

B. H. Chong, “Primary immune thrombocytopenia: Understanding pathogenesis is the key to better treatments,” J. Thromb. Haemost., vol. 7, no. 2, pp. 319–321, 2009, doi: 10.1111/j.1538-7836.2008.03258.x.

H. Sukati, H. G. Watson, S. J. Urbaniak, and R. N. Barker, “Mapping helper T-cell epitopes on platelet membrane glycoprotein IIIa in chronic autoimmune thrombocytopenic purpura,” Blood, vol. 109, no. 10, pp. 4528–4538, 2007, doi: 10.1182/blood-2006-09-044388.

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.

R. Spolski and W. J. Leonard, “Interleukin-21: A double-edged sword with therapeutic potential,” Nat. Rev. Drug Discov., vol. 13, no. 5, pp. 379–395, 2014, doi: 10.1038/nrd4296.

J. Parrish-novak, S. R. Dillon, and D. Foster, “and regulation of lymphocyte function,” pp. 1–8, 2000.

I. Peluso et al., “IL-21 counteracts the regulatory T cell-mediated suppression of human CD4+ T lymphocytes,” J. Immunol., vol. 178, no. 2, pp. 732–739, Jan. 2007, doi: 10.4049/JIMMUNOL.178.2.732.

X. Niu et al., “IL-21 regulates Th17 cells in rheumatoid arthritis,” Hum. Immunol., vol. 71, no. 4, pp. 334–341, 2010, doi: 10.1016/j.humimm.2010.01.010.

K. Ozaki et al., “A critical role for IL-21 in regulating immunoglobulin production,” Science (80-. )., vol. 298, no. 5598, pp. 1630–1634, 2002, doi: 10.1126/science.1077002.

X. Yao, C. Li, J. Yang, C. Li, and Y. Xia, “Differences in frequency and regulation of T follicular helper cells between newly diagnosed and chronic pediatric immune thrombocytopenia,” Blood Cells, Mol. Dis., vol. 61, no. October, pp. 26–36, 2016, doi: 10.1016/j.bcmd.2016.06.006.

S. Wang et al., “Reduced PTEN involved in primary immune thrombocytopenia via contributing to B cell hyper-responsiveness,” Mol. Immunol., vol. 93, no. January, pp. 144–151, 2018, doi: 10.1016/j.molimm.2017.11.010.

D. B. Cines, A. Cuker, and J. W. Semple, “Pathogenesis of immune thrombocytopenia,” Press. Medicale, vol. 43, no. 4P2, p. 24630266, 2014, doi: 10.1016/j.lpm.2014.01.010.

J. Johnsen, “Pathogenesis in immune thrombocytopenia: new insights.,” Hematology Am. Soc. Hematol. Educ. Program, vol. 2012, pp. 306–312, 2012, doi: 10.1182/asheducation.v2012.1.306.3798320.

J. W. Semple, D. Provan, M. B. Garvey, and J. Freedman, “Recent progress in understanding the pathogenesis of immune thrombocytopenia,” Curr. Opin. Hematol., vol. 17, no. 6, pp. 590–595, 2010, doi: 10.1097/MOH.0b013e32833eaef3.

M. Disorders, “Fe rra ta St or ti Fo u nd at io n Fe rra ta St or ti Fo u,” Haematologica, vol. 91, no. 9, pp. 2007–2009, 2006, [Online]. Available: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16963398.

B. Olsson et al., “T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura,” Nat. Med., vol. 9, no. 9, pp. 1123–1124, 2003, doi: 10.1038/nm921.

K. Kałwak et al., “Late-onset idiopathic thrombocytopenic purpura correlates with rapid B-cell recovery after allogeneic T-cell-depleted peripheral blood progenitor cell transplantation in children,” Transplant. Proc., vol. 34, no. 8, pp. 3374–3377,2002, doi:10.1016/S0041-1345(02)03607-2.

R. Stasi et al., “Response to B-cell-depleting therapy with rituximab reverts the abnormalities of T-cell subsets in patients with idiopathic thrombocytopenic purpura,” Blood, vol. 110, no. 8, pp. 2924–2930, 2007, doi: 10.1182/blood-2007-02-068999.

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.

S. Crotty, “Follicular Helper CD4 T cells (T FH),” Annu. Rev. Immunol., vol. 29, pp. 621–663, 2011, doi: 10.1146/annurev-immunol-031210-101400.

H. Manku, T. J. Vyse, G. Roncador, and G. A. Huttley, “Institutional Login ,” pp. 21–23, 2009.

J. Ma et al., “Increased frequency of circulating follicular helper T cells in patients with rheumatoid arthritis,” Clin. Dev. Immunol., vol. 2012, 2012, doi: 10.1155/2012/827480.

K. Szabo, G. Papp, S. Barath, E. Gyimesi, A. Szanto, and M. Zeher, “Follicular helper T cells may play an important role in the severity of primary Sjögren’s syndrome,” Clin. Immunol., vol. 147, no. 2, pp. 95–104, 2013, doi: 10.1016/j.clim.2013.02.024.

C. Zhu et al., “Increased frequency of follicular helper T cells in patients with autoimmune thyroid disease,” J. Clin. Endocrinol. Metab., vol. 97, no. 3, pp. 943–950, 2012, doi: 10.1210/jc.2011-2003.