Heavy-chain subclass of round antiplatelet IgG in autoimmune thrombocytopenic purpura

Hymes, K; Schur, P H; Karpatkin, S

doi:10.1182/blood.v56.1.84.bloodjournal56184

Cited by 4 publications

(5 citation statements)

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“…Mature megakaryocytes eventually release pro‐platelets into the bloodstream which eventually become circulating platelets . In ITP, although antibody‐mediated peripheral destruction of platelets was the earliest manifestation discovered, it is now known that platelet production from megakaryocytes in ITP is defective and this contributes to the thrombocytopenia in patients, but little is known of how reduced platelet production in the bone marrow is mediated.…”

Section: Discussionmentioning

confidence: 99%

Antiplatelet antibody‐induced thrombocytopenia does not correlate with megakaryocyte abnormalities in murine immune thrombocytopenia

et al. 2018

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Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by increased peripheral immune platelet destruction and megakaryocyte defects in the bone marrow. Although ITP was originally thought to be primarily due to antibody-mediated autoimmunity, it is now clear that T cells also play a significant role in the disease. However, the exact interplay between platelet destruction, megakaryocyte dysfunction and the elements of both humoral and cell-mediated immunity in ITP remains incompletely defined. While most studies have focused on immune platelet destruction in the spleen, an additional possibility is that the antiplatelet antibodies can also destroy bone marrow megakaryocytes. To address this, we negated the effects of T cells by utilizing an in vivo passive ITP model where BALB/c mice were administered various anti-αIIb, anti-β3 or anti-GPIb antibodies or antisera and platelet counts and bone marrow megakaryocytes were enumerated. Our results show that after 24 hours, all the different antiplatelet antibodies/sera induced variable degrees of thrombocytopenia in recipient mice. Compared with naïve control mice, however, histological examination of the bone marrow revealed that only 2 antibody preparations (mouse-anti-mouse β3 sera and an anti- αIIb monoclonal antibody (MWReg30) could affect bone marrow megakaryocyte counts. Our study shows that while most antiplatelet antibodies induce acute thrombocytopenia, the majority of them do not affect the number of megakaryocytes in the bone marrow. This suggests that other mechanisms may be responsible for megakaryocyte abnormalities seen during immune thrombocytopenia.

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Section: Discussionmentioning

confidence: 99%

Antiplatelet antibody‐induced thrombocytopenia does not correlate with megakaryocyte abnormalities in murine immune thrombocytopenia

et al. 2018

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“…IgM antibodies were shown to fix complement on platelets which could facilitate clearance, but this has not been further investigated; IgG autoantibodies seem to be the main mediator of antibody-driven autoimmunity ( 100 ). Most prevalent are IgGs of the IgG1 subclass, and while IgG2, IgG3, and IgG4 subclass autoantibodies can be also found in patients, they are often accompanied by IgG1 antibodies ( 103 , 104 ). Autoantibody allotypes and Fc-glycosylation are important determinants in antibody-mediated immunity and immunological disorders related to ITP ( 105 – 107 ), yet have been scarcely investigated.…”

Section: Etiologymentioning

confidence: 99%

Emerging Concepts in Immune Thrombocytopenia

et al. 2018

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Immune thrombocytopenia (ITP) is an autoimmune disease defined by low platelet counts which presents with an increased bleeding risk. Several genetic risk factors (e.g., polymorphisms in immunity-related genes) predispose to ITP. Autoantibodies and cytotoxic CD8+ T cells (Tc) mediate the anti-platelet response leading to thrombocytopenia. Both effector arms enhance platelet clearance through phagocytosis by splenic macrophages or dendritic cells and by induction of apoptosis. Meanwhile, platelet production is inhibited by CD8+ Tc targeting megakaryocytes in the bone marrow. CD4+ T helper cells are important for B cell differentiation into autoantibody secreting plasma cells. Regulatory Tc are essential to secure immune tolerance, and reduced levels have been implicated in the development of ITP. Both Fcγ-receptor-dependent and -independent pathways are involved in the etiology of ITP. In this review, we present a simplified model for the pathogenesis of ITP, in which exposure of platelet surface antigens and a loss of tolerance are required for development of chronic anti-platelet responses. We also suggest that infections may comprise an important trigger for the development of auto-immunity against platelets in ITP. Post-translational modification of autoantigens has been firmly implicated in the development of autoimmune disorders like rheumatoid arthritis and type 1 diabetes. Based on these findings, we propose that post-translational modifications of platelet antigens may also contribute to the pathogenesis of ITP.

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“…The ratio of the different subclasses of IgG bound to ITP and normal platelets is identical to the proportion of each subclass in normal serum. 78,171 The concentration of platelet bound IgG-I is highest, followed by subclasses 2, 3, and 4. This subclass distribution is similar to the subclass of antierythrocyte autoantibodies measured in patients with autoimmune hemolytic anemia.…”

Section: Subclass Of Igg On the Plateletmentioning

confidence: 99%

“…One recently described assay that measures total PAIgG is that described by Hymes and coworkers. 78 Test platelets are washed and lysed by freeze-thawing and sonication. The IgG from the platelet supernatant is bound to the walls of plastic microtiter plates and after the removal of unbound protein by washing, a known concentration of anti-IgG is added for another incubation and the unbound antisera is removed by washing.…”

Section: Measurement Of Igg From Platelet Lysatesmentioning

confidence: 99%