Antibody Against Megakaryocytes in Idiopathic Thrombocytopenic Purpura

McMillan, R. S.; Luiken, George A.; Levy, Richard J.; Yelenosky, Robert; Longmire, Robert L.

doi:10.1001/jama.1978.03280500056020

Cited by 53 publications

(43 citation statements)

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“…During maturation, MK express CD41/CD61 and CD42b/CD42a on their surfaces, 6,7,26 so it is likely that the binding of antiplatelet autoantibodies could inhibit MK maturation [27][28][29] and interfere with platelet release. During endomitosis, the ploidy of diploid (2N) MK precursors increases 30 and each of these mature MK is able to release thousands of platelets 31 by extending proplatelets.…”

Section: Discussionmentioning

confidence: 99%

Immune thrombocytopenia: antiplatelet autoantibodies inhibit proplatelet formation by megakaryocytes and impair platelet production in vitro

et al. 2015

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ABSTRACTdecreased the number of proplatelet-bearing MK and hence the number of platelets released in culture, without altering MK proliferation, differentiation or apoptosis. A small subset of sera decreased MK numbers, inhibited maturation and enhanced caspase activation, but the corresponding patients' IgG did not recapitulate these effects. Notably, TPO-R agonists were able to overcome the inhibitory effect of several ITP antibodies on MK by enhancing their capacity to form proplatelets.

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Section: Discussionmentioning

confidence: 99%

Immune thrombocytopenia: antiplatelet autoantibodies inhibit proplatelet formation by megakaryocytes and impair platelet production in vitro

et al. 2015

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“…15 It is not surprising that ITP autoantibody might affect platelet production because it has been well shown that the common ITP autoantigens, GPIIb-IIIa and GPIb-IX, are expressed on the surfaces of megakaryocytes 7 and that ITP autoantibody binds to megakaryocytes. 16,17 Attempts to use megakaryocyte colony formation to study thrombopoiesis in ITP have given contradictory results. Some groups, culturing ITP bone marrow, have found increased numbers of megakaryocyte colony-forming units (CFU-Ms), 18,19 whereas others have found decreased numbers of CFU-Ms. 20 Similarly, one group 21 reported that ITP plasma did not affect CFU-M formation by normal cells, yet another group 18 noted increased CFU-M formation in the presence of ITP serum.…”

Section: Discussionmentioning

confidence: 99%

Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult patients with chronic ITP

McMillan

Wang²,

Tomer³

et al. 2004

Blood

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481

319

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Chronic immune thrombocytopenic purpura (ITP) is manifested by autoantibodyinduced platelet destruction. Platelet turnover studies suggest that autoantibody may also affect platelet production. To evaluate this, we studied the effect of plasma from adult patients with chronic ITP on in vitro megakaryocyte production. CD34 ؉ cells, obtained from healthy donors, were cultured in medium containing PEG-rHuMGDF and 10% plasma from either ITP patients or healthy subjects. Cultures containing plasma from 12 of 18 ITP patients showed a significant decrease (26%-95%) in megakaryocyte production when compared with control cultures. Positive ITP plasmas not only reduced the total number of megakaryocytes produced during the culture period but also inhibited megakaryocyte maturation, resulting in fewer 4N, 8N, and 16N cells. The role of antibody in this suppression is supported by 2 factors: (1) immunoglobulin G (IgG) from ITP patients inhibited megakaryocyte production when compared with control IgG; and (2) adsorption of autoantibody, using immobilized antigen, resulted in significantly less inhibition of megakaryocyte production when compared with unadsorbed plasma. These results show that plasma autoantibody from some adult patients with ITP inhibits in vitro megakaryocyte production, suggesting that a similar effect may occur in vivo. IntroductionIn 1950, Dr William Harrington was infused with blood from a patient with chronic immune thrombocytopenic purpura (ITP), resulting in the rapid onset of severe thrombocytopenia. He recovered within the next few days. Further studies by Harrington et al 1 and Shulman et al 2 showed clearly that patients with chronic ITP have a circulating factor capable of destroying homologous and autologous platelets. The severity of the thrombocytopenia was dose dependent, and the plasma factor could be adsorbed by platelets and was present in the immunoglobulin G (IgG)-rich fraction after ion-exchange chromatography. For the next several years, it was concluded that thrombocytopenia in patients with chronic ITP was caused solely by autoantibody-induced platelet destruction.However, in the early 1980s, autologous platelet survival studies from several laboratories showed that in approximately two thirds of ITP patients, platelet turnover is either reduced or normal, not increased, as would be expected if platelet destruction were the only mechanism causing thrombocytpenia. [3][4][5][6] Because megakaryocytes express GPIIb-IIIa and GPIb-IX on their surfaces during maturation 7 and because most ITP autoantibodies react with one or both of these glycoprotein complexes, 8,9 it follows that autoantibody binding to megakaryocytes could interfere with platelet production and release from the bone marrow either by causing intramedullary megakaryocyte or platelet destruction or by interfering with megakaryocyte maturation.Recently, Chang et al 10 evaluated the effect of plasma, from patients with childhood ITP (44 with acute ITP and 9 with chronic ITP), on thrombopoietin-induced production of megaka...

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“…Nevertheless, some studies revealed autoantibodies binding to either platelets intramedullary or megakaryocytes [29], thus affecting thrombopoiesis [30,31].…”

Section: Discussionmentioning

confidence: 99%

Thrombopenic purpura induced by a monoclonal antibody directed to a 35-kilodalton surface protein (p35) expressed on murine platelets and endothelial cells

Rodríguez‐Calvillo

Gabari

Duarte

et al. 2001

Experimental Hematology

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Objective. With the aim of obtaining monoclonal antibodies (mAbs) against mouse endothelial surface antigens, immunization of rats with a mouse-derived endothelial cell line (PY4.1) and subsequent hybridoma production were performed. Materials and Methods. One of the mAbs produced by hybridoma EOL5F5 was selected for its surface binding to endothelial cell lines, and identification of the mAb-recognized antigen was performed by immunoprecipitation. Experiments were performed to analyze the effects of EOL5F5 on systemic administration to mice. Results. EOL5F5-recognized antigen was a single band of 35 kDa under reducing and nonreducing conditions, features that do not match other known differentiation antigens with comparable tissue distribution. In vivo administration of purified EOL5F5 mAb to mice (n ϭ 20) induced intense cutaneous purpura as well as severe but transient thrombocytopenia. Expression of EOL5F5-recognized antigen was detected on platelets from which it immunoprecipitated a moiety of identical electrophoretic pattern in SDS-PAGE, as the one recognized on endothelial cells. Immunohistochemically, EOL5F5-recognized antigen (p35) also was expressed on dermal capillaries, suggesting that, in addition to thrombocytopenia, damaging effects of the antibody on endothelial cells also might cause the observed purpura. Conclusions. Our results show induction of thrombocytopenic purpura in mice with an mAb against a single antigenic determinant expressed on both platelets and endothelium. EOL5F5 mAb injection sets the stage for useful experimental models that resemble immune thrombocytopenic purpura.

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Antibody Against Megakaryocytes in Idiopathic Thrombocytopenic Purpura

Abstract: (30-

Cited by 53 publications

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Immune thrombocytopenia: antiplatelet autoantibodies inhibit proplatelet formation by megakaryocytes and impair platelet production in vitro

Immune thrombocytopenia: antiplatelet autoantibodies inhibit proplatelet formation by megakaryocytes and impair platelet production in vitro

Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult patients with chronic ITP

Thrombopenic purpura induced by a monoclonal antibody directed to a 35-kilodalton surface protein (p35) expressed on murine platelets and endothelial cells

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