Advances in immunopathogenesis of adult immune thrombocytopenia

Xinguang Liu , Yu Hou , Jun Peng

Front. Med. ›› 2013, Vol. 7 ›› Issue (4) : 418 -424.

PDF (207KB)
Front. Med. ›› 2013, Vol. 7 ›› Issue (4) : 418 -424. DOI: 10.1007/s11684-013-0297-8
REVIEW
REVIEW

Advances in immunopathogenesis of adult immune thrombocytopenia

Author information +
History +
PDF (207KB)

Abstract

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by immune-mediated accelerated platelet destruction and/or suppressed platelet production. Although the development of autoantibodies against platelet glycoproteins remains central in the pathophysiology of ITP, several abnormalities involving the cellular mechanisms of immune modulation have been identified, and the pathways behind the immune-mediated destruction of platelets have opened new avenues for the design of specific immunotherapies in an attempt to reduce the platelet destruction. This review is primarily focused on the recent literature with respect to immunopathological mechanisms in patients with ITP.

Keywords

primary immune thrombocytopenia / B lymphocytes / T lymphocytes / antigen-presenting cells / cytokines

Cite this article

Download citation ▾
Xinguang Liu, Yu Hou, Jun Peng. Advances in immunopathogenesis of adult immune thrombocytopenia. Front. Med., 2013, 7(4): 418-424 DOI:10.1007/s11684-013-0297-8

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, Chong BH, Cines DB, Gernsheimer TB, Godeau B, Grainger J, Greer I, Hunt BJ, Imbach PA, Lyons G, McMillan R, Rodeghiero F, Sanz MA, Tarantino M, Watson S, Young J, Kuter DJ. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood2010; 115(2): 168-186

[2]

Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, Bussel JB, Cines DB, Chong BH, Cooper N, Godeau B, Lechner K, Mazzucconi MG, McMillan R, Sanz MA, Imbach P, Blanchette V, Kühne T, Ruggeri M, George JN. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood2009; 113(11): 2386-2393

[3]

Segal JB, Powe NR. Prevalence of immune thrombocytopenia: analyses of administrative data. J Thromb Haemost2006; 4(11): 2377-2383

[4]

Terrell DR, Beebe LA, Vesely SK, Neas BR, Segal JB, George JN. The incidence of immune thrombocytopenic purpura in children and adults: a critical review of published reports. Am J Hematol2010; 85(3): 174-180

[5]

Terrell DR, Beebe LA, Neas BR, Vesely SK, Segal JB, George JN. Prevalence of primary immune thrombocytopenia in Oklahoma. Am J Hematol2012; 87(9): 848-852

[6]

Harrington WJ, Sprague CC, Minnich V, Moore CV, Aulvin RC, Dubach R. Immunologic mechanisms in idiopathic and neonatal thrombocytopenic purpura. Ann Intern Med1953; 38(3): 433-469

[7]

Kiefel V, Freitag E, Kroll H, Santoso S, Mueller-Eckhardt C. Platelet autoantibodies (IgG, IgM, IgA) against glycoproteins IIb/IIIa and Ib/IX in patients with thrombocytopenia. Ann Hematol1996; 72(4): 280-285

[8]

Roark JH, Bussel JB, Cines DB, Siegel DL. Genetic analysis of autoantibodies in idiopathic thrombocytopenic purpura reveals evidence of clonal expansion and somatic mutation. Blood2002; 100(4): 1388-1398

[9]

Gu D, Ge J, Du W, Xue F, Chen Z, Zhao H, Zhou Z, Xu J, Liu P, Zhao Q, Zhang L, Yang R. Raised expression of APRIL in Chinese patients with immune thrombocytopenia and its clinical implications. Autoimmunity2009; 42(8): 692-698

[10]

Zhu XJ, Shi Y, Peng J, Guo CS, Shan NN, Qin P, Ji XB, Hou M. The effects of BAFF and BAFF-R-Fc fusion protein in immune thrombocytopenia. Blood2009; 114(26): 5362-5367

[11]

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 Med2003; 9(9): 1123-1124

[12]

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. Eur J Haematol2006; 76(5): 427-431

[13]

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. Haematologica2008; 93(9): 1428-1430

[14]

Semple JW, Provan D. The immunopathogenesis of immune thrombocytopenia: T cells still take center-stage. Curr Opin Hematol2012; 19(5): 357-362

[15]

Peng J, Liu C, Liu D, Ren C, Li W, Wang Z, Xing N, Xu C, Chen X, Ji C, Zhang M, Hou M. Effects of B7-blocking agent and/or CsA on induction of platelet-specific T-cell anergy in chronic autoimmune thrombocytopenic purpura. Blood2003; 101(7): 2721-2726

[16]

Zhang XL, Peng J, Sun JZ, Guo CS, Yu Y, Wang ZG, Chu XX, Hou M. Modulation of immune response with cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin-induced anergic T cells in chronic idiopathic thrombocytopenic purpura. J Thromb Haemost2008; 6(1): 158-165

[17]

Zhu X, Zhu P, Guo XL. T cell repertoires correlate with pathogenesis of chronic idiopathic thrombocytopenic purpura.Natl Med J China (Zhonghua Yi Xue Za Zhi)2005; 85(47): 3316-3322 (in Chinese)

[18]

Fogarty PF, Rick ME, Zeng W, Risitano AM, Dunbar CE, Bussel JB. T cell receptor VB repertoire diversity in patients with immune thrombocytopenia following splenectomy. Clin Exp Immunol2003; 133(3): 461-466

[19]

Wang T, Zhao H, Ren H, Guo J, Xu M, Yang R, Han ZC. Type 1 and type 2 T-cell profiles in idiopathic thrombocytopenic purpura. Haematologica2005; 90(7): 914-923

[20]

Panitsas FP, Theodoropoulou M, Kouraklis A, Karakantza M, Theodorou GL, Zoumbos NC, Maniatis A, Mouzaki A. Adult chronic idiopathic thrombocytopenic purpura (ITP) is the manifestation of a type-1 polarized immune response. Blood2004; 103(7): 2645-2647

[21]

Guo C, Chu X, Shi Y, He W, Li L, Wang L, Wang Y, Peng J, Hou M. Correction of Th1-dominant cytokine profiles by high-dose dexamethasone in patients with chronic idiopathic thrombocytopenic purpura. J Clin Immunol2007; 27(6): 557-562

[22]

Zhang J, Ma D, Zhu X, Qu X, Ji C, Hou M. Elevated profile of Th17, Th1 and Tc1 cells in patients with immune thrombocytopenic purpura. Haematologica2009; 94(9): 1326-1329

[23]

Cao J, Li XQ, Chen C, Zeng LY, Cheng H, Li ZY, Pang XY, Xu KL. Imbalance of Th17/Treg cells ratio in peripheral blood of patients with immune thrombocytopenia. J Exp Hematol (Zhongguo Shi Yan Xue Ye Xue Za Zhi)2011; 19(3): 730-733 (in Chinese)

[24]

Saitoh T, Tsukamoto N, Koiso H, Mitsui T, Yokohama A, Handa H, Karasawa M, Ogawara H, Nojima Y, Murakami H. Interleukin-17F gene polymorphism in patients with chronic immune thrombocytopenia. Eur J Haematol2011; 87(3): 253-258

[25]

Rocha AM, Souza C, Rocha GA, de Melo FF, Clementino NC, Marino MC, Bozzi A, Silva ML, Martins Filho OA, Queiroz DM. The levels of IL-17A and of the cytokines involved in Th17 cell commitment are increased in patients with chronic immune thrombocytopenia. Haematologica2011; 96(10): 1560-1564

[26]

Cao J, Chen C, Zeng L, Li L, Li X, Li Z, Xu K. Elevated plasma IL-22 levels correlated with Th1 and Th22 cells in patients with immune thrombocytopenia. Clin Immunol2011; 141(1): 121-123

[27]

Hu Y, Li H, Zhang L, Shan B, Xu X, Li H, Liu X, Xu S, Yu S, Ma D, Peng J, Hou M. Elevated profiles of Th22 cells and correlations with Th17 cells in patients with immune thrombocytopenia. Hum Immunol2012; 73(6): 629-635

[28]

Cao J, Chen C, Li L, Zeng L, Li Z, Yan Z, Chen W, Cheng H, Sang W, Xu K. Effects of high-dose dexamethasone on regulating interleukin-22 production and correcting Th1 and Th22 polarization in immune thrombocytopenia. J Clin Immunol2012; 32(3): 523-529

[29]

Vignali DA, Collison LW, Workman CJ. How regulatory T cells work. Nat Rev Immunol2008; 8(7): 523-532

[30]

Collison LW, Workman CJ, Kuo TT, Boyd K, Wang Y, Vignali KM, Cross R, Sehy D, Blumberg RS, Vignali DA. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature2007; 450(7169): 566-569

[31]

Liu B, Zhao H, Poon MC, Han Z, Gu D, Xu M, Jia H, Yang R, Han ZC. Abnormality of CD4(+)CD25(+) regulatory T cells in idiopathic thrombocytopenic purpura. Eur J Haematol2007; 78(2): 139-143

[32]

Ling Y, Cao X, Yu Z, Ruan C. 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 Haematol2007; 79(4): 310-316

[33]

Yu J, Heck S, Patel V, Levan J, Yu Y, Bussel JB, Yazdanbakhsh K. Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura. Blood2008; 112(4): 1325-1328

[34]

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. Thromb Res2007; 120(2): 187-193

[35]

Stasi R, Cooper N, Del Poeta G, Stipa E, Laura Evangelista M, Abruzzese E, Amadori S. Analysis of regulatory T-cell changes in patients with idiopathic thrombocytopenic purpura receiving B cell-depleting therapy with rituximab. Blood2008; 112(4): 1147-1150

[36]

Bao W, Bussel JB, Heck S, He W, Karpoff M, Boulad N, Yazdanbakhsh K. Improved regulatory T-cell activity in patients with chronic immune thrombocytopenia treated with thrombopoietic agents. Blood2010; 116(22): 4639-4645

[37]

Zhang XL, Peng J, Sun JZ, Liu JJ, Guo CS, Wang ZG, Yu Y, Shi Y, Qin P, Li SG, Zhang LN, Hou M. De novo induction of platelet-specific CD4(+)CD25(+) regulatory T cells from CD4(+)CD25(-) cells in patients with idiopathic thrombocytopenic purpura. Blood2009; 113(11): 2568-2577

[38]

Shenoy S, Mohanakumar T, Chatila T, Tersak J, Duffy B, Wang R, Thilenius AR, Russell JH. Defective apoptosis in lymphocytes and the role of IL-2 in autoimmune hematologic cytopenias. Clin Immunol2001; 99(2): 266-275

[39]

Olsson B, Andersson PO, Jacobsson S, Carlsson L, Wadenvik H. Disturbed apoptosis of T-cells in patients with active idiopathic thrombocytopenic purpura. Thromb Haemost2005; 93(1): 139-144

[40]

Li X, Zhong H, Bao W, Boulad N, Evangelista J, Haider MA, Bussel J, Yazdanbakhsh K. Defective regulatory B-cell compartment in patients with immune thrombocytopenia. Blood2012; 120(16): 3318-3325

[41]

Mauri C, Bosma A. Immune regulatory function of B cells. Annu Rev Immunol2012; 30(1): 221-241

[42]

Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K. Development of monocytes, macrophages, and dendritic cells. Science2010; 327(5966): 656-661

[43]

Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med2002; 346(13): 995-1008

[44]

Kuwana M, Okazaki Y, Ikeda Y. Splenic macrophages maintain the anti-platelet autoimmune response via uptake of opsonized platelets in patients with immune thrombocytopenic purpura. J Thromb Haemost2009; 7(2): 322-329

[45]

Liu XG, Ma SH, Sun JZ, Ren J, Shi Y, Sun L, Dong XY, Qin P, Guo CS, Hou M, Peng J. High-dose dexamethasone shifts the balance of stimulatory and inhibitory Fcγ receptors on monocytes in patients with primary immune thrombocytopenia. Blood2011; 117(6): 2061-2069

[46]

Asahi A, Nishimoto T, Okazaki Y, Suzuki H, Masaoka T, Kawakami Y, Ikeda Y, Kuwana M. Helicobacter pylori eradication shifts monocyte Fcgamma receptor balance toward inhibitory FcγRIIB in immune thrombocytopenic purpura patients. J Clin Invest2008; 118(8): 2939-2949

[47]

Wu Z, Zhou J, Prsoon P, Wei X, Liu X, Peng B. Low expression of FCGRIIB in macrophages of immune thrombocytopenia-affected individuals. Int J Hematol2012; 96(5): 588-593

[48]

Hamzeh-Cognasse H, Cognasse F, Palle S, Chavarin P, Olivier T, Delézay O, Pozzetto B, Garraud O. Direct contact of platelets and their released products exert different effects on human dendritic cell maturation. BMC Immunol2008; 9(1): 54

[49]

Garcia-Suarez J, Prieto A, Reyes E, Manzano L, Merino JL, Alvarez-Mon M. Severe chronic autoimmune thrombocytopenic purpura is associated with an expansion of CD56+ CD3- natural killer cells subset. Blood1993; 82(5): 1538-1545

[50]

Gernsheimer T. Chronic idiopathic thrombocytopenic purpura: mechanisms of pathogenesis. Oncologist2009; 14(1): 12-21

[51]

Van Wyk V, Kotzé HF, Heyns AP. Kinetics of indium-111-labelled platelets in HIV-infected patients with and without associated thrombocytopaenia. Eur J Haematol1999; 62(5): 332-335

[52]

Ballem PJ, Segal GM, Stratton JR, Gernsheimer T, Adamson JW, Slichter SJ. Mechanisms of thrombocytopenia in chronic autoimmune thrombocytopenic purpura. Evidence of both impaired platelet production and increased platelet clearance. J Clin Invest1987; 80(1): 33-40

[53]

Jenkins JM, Williams D, Deng Y, Uhl J, Kitchen V, Collins D, Erickson-Miller CL. Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist. Blood2007; 109(11): 4739-4741

[54]

Chang M, Nakagawa PA, Williams SA, Schwartz MR, Imfeld KL, Buzby JS, Nugent DJ. Immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies inhibit megakaryocytopoiesis in vitro. Blood2003; 102(3): 887-895

[55]

McMillan R, Wang L, Tomer A, Nichol J, Pistillo J. Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult patients with chronic ITP. Blood2004; 103(4): 1364-1369

[56]

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. Blood2010; 116(20): 4307-4316

[57]

Benedetti F, de Sabata D, Perona G. T suppressor activated lymphocytes (CD8+/DR+) inhibit megakaryocyte progenitor cell differentiation in a case of acquired amegakaryocytic thrombocytopenic purpura. Stem Cells1994; 12(2): 205-213

[58]

Li S, Wang L, Zhao C, Li L, Peng J, Hou M. CD8+ T cells suppress autologous megakaryocyte apoptosis in idiopathic thrombocytopenic purpura. Br J Haematol2007; 139(4): 605-611

[59]

Cohen-Solal K, Villeval JL, Titeux M, Lok S, Vainchenker W, Wendling F. Constitutive expression of Mpl ligand transcripts during thrombocytopenia or thrombocytosis. Blood1996; 88(7): 2578-2584

[60]

Kuter DJ. New thrombopoietic growth factors. Blood2007; 109(11): 4607-4616

[61]

Gu J, Lu L, Xu R, Chen X. Plasma thrombopoietin levels in patients with aplastic anemia and idiopathic thrombocytopenic purpura. Chin Med J (Engl)2002; 115(7): 983-986

[62]

von dem Borne A, Folman C, van den Oudenrijn S, Linthorst G, de Jong S, de Haas M. The potential role of thrombopoietin in idiopathic thrombocytopenic purpura. Blood Rev2002; 16(1): 57-59

[63]

Wang B, Nichol JL, Sullivan JT. Pharmacodynamics and pharmacokinetics of AMG 531, a novel thrombopoietin receptor ligand. Clin Pharmacol Ther2004; 76(6): 628-638

[64]

Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM, Aledort LM, George JN, Kessler CM, Sanz MA, Liebman HA, Slovick FT, de Wolf JT, Bourgeois E, Guthrie TH Jr, Newland A, Wasser JS, Hamburg SI, Grande C, Lefrère F, Lichtin AE, Tarantino MD, Terebelo HR, Viallard JF, Cuevas FJ, Go RS, Henry DH, Redner RL, Rice L, Schipperus MR, Guo DM, Nichol JL. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet2008; 371(9610): 395-403

[65]

Erickson-Miller CL, DeLorme E, Tian SS, Hopson CB, Stark K, Giampa L, Valoret EI, Duffy KJ, Luengo JL, Rosen J, Miller SG, Dillon SB, Lamb P. Discovery and characterization of a selective, nonpeptidyl thrombopoietin receptor agonist. Exp Hematol2005; 33(1): 85-93

[66]

Bussel JB, Provan D, Shamsi T, Cheng G, Psaila B, Kovaleva L, Salama A, Jenkins JM, Roychowdhury D, Mayer B, Stone N, Arning M. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet2009; 373(9664): 641-648

[67]

Wang S, Yang R, Zou P, Hou M, Wu D, Shen Z, Lu X, Li Y, Chen X, Niu T, Sun H, Yu L, Wang Z, Zhang Y, Chang N, Zhang G, Zhao Y. A multicenter randomized controlled trial of recombinant human thrombopoietin treatment in patients with primary immune thrombocytopenia. Int J Hematol2012; 96(2): 222-228

RIGHTS & PERMISSIONS

Higher Education Press and Springer-Verlag Berlin Heidelberg

AI Summary AI Mindmap
PDF (207KB)

3954

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/