Extracellular epitopes of platelet glycoprotein Ib alpha reactive with serum antibodies from patients with chronic idiopathic thrombocytopenic purpura

He, Ruyi; Reid, D. M.; Jones, CE; Shulman, N. Raphael

doi:10.1182/blood.v86.10.3789.bloodjournal86103789

Cited by 43 publications

(20 citation statements)

References 35 publications

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“…The present studies show that PAAb from 20 of 28 patients with chronic ITP are either completely or partially light chain restricted, adding further support for autoantibody clonality in chronic ITP. The presence of autoantibody clonality in ITP is consistent with several previous observations suggesting that ITP patients have a limited antigenic repertoire (14)(15)(16)(17)(18).…”

Section: Discussionsupporting

confidence: 91%

Clonal Restriction of Platelet-associated Anti-GPIIb/IIIa Autoantibodies in Patients with Chronic ITP

McMillan

Lopez-Dee²,

Bowditch³

2001

Thromb Haemost

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Chronic immune thrombocytopenic purpura is due to platelet destruction induced by autoantibodies against platelet surface antigens. Prior studies show that some serum autoantibodies are light-chain restricted, suggesting a clonal origin. Since plasma and plateletassociated antibody from the same patient may bind to different epitopes, it is important to evaluate the clonality of platelet-associated antibody. Platelet-associated autoantibodies from 28 ITP patients were studied. Of 23 platelet-associated antibodies tested directly, 16 showed significant light chain restriction (7 complete and 9 partial) when compared to plasma IgG light chain distribution. Similarly, 9 of 12 platelet-associated antibody eluates were light chain restricted, 5 complete and 4 partial. In all cases where platelet-associated antibody and antibody eluate from the same patient were studied, the results were concordant. We conclude that a significant proportion of plateletassociated antibodies from ITP patients show apparent clonality, as evaluated by light chain restriction. These results are consistent with other studies in ITP suggesting a limited antigenic repertoire.

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Section: Discussionsupporting

confidence: 91%

Clonal Restriction of Platelet-associated Anti-GPIIb/IIIa Autoantibodies in Patients with Chronic ITP

McMillan

Lopez-Dee²,

Bowditch³

2001

Thromb Haemost

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“…These GP immobilization assays (phase III assays) measure platelet GP‐specific antiplatelet autoantibodies and have overcome the problems of non‐specific immune and non‐immune IgG interference associated with the traditional assays used to measure platelet‐associated IgG (Kelton, 1995; McMillan, 1995). Several lines of investigation suggest that the antigen repertoire in chronic ITP may be limited (He et al , 1995; Hou et al , 1995; Bowditch et al , 1996; Warner & Kelton, 1997; Escher et al , 1998). This implies that the autoantibodies in ITP are restricted to a limited number of regions on GPIIb/IIIa or Ib/IX/V.…”

mentioning

confidence: 99%

The IgG subclasses of platelet‐associated autoantibodies directed against platelet glycoproteins IIb/IIIa in patients with idiopathic thrombocytopenic purpura

Chan¹,

Moore²,

Finch

et al. 2003

Br J Haematol

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Summary. The majority of patients with idiopathic thrombocytopenic purpura (ITP) have antiplatelet autoantibodies that are most frequently directed against platelet glycoproteins IIb/IIIa or Ib/IX/V. However, there is some debate whether the immune response is oligoclonal or polyclonal in nature. We investigated the subclass distribution of anti-IIb/IIIa IgG autoantibodies in 59 prospectively studied patients with ITP. We also tested patients with a variety of thrombocytopenic disorders (n ¼ 31) and healthy controls (n ¼ 30). Platelet lysates were tested for IgG anti-IIb/IIIa autoantibodies, and the specific IgG subclass distribution was measured using antigen capture assays. All testing was done blinded to diagnosis and other assay results. After unblinding, we found that 43 of the 59 ITP patients had anti-IIb/IIIa autoantibodies (sensitivity ¼ 73%). Anti-IIb/IIIa autoantibodies were also detected in five of the 31 non-ITP patients, but in none of the 30 healthy controls (specificity ¼ 91%). The IgG subclass assay was positive in 39 of the 43 ITP patients with anti-IIb/IIIa antibodies (sensitivity ¼ 92%) and in 12 samples that had no detectable anti-IIb/IIIa antibodies including two ITP patients (specificity ¼ 83%). The most common subclass in the ITP patient samples was IgG1 (77%), either alone (n ¼ 14) or with other IgG subclass antibodies (n ¼ 19). However, there were also patients with only IgG2 (n ¼ 2), IgG3 (n ¼ 3) or IgG4 (n ¼ 3) antibodies. Our results are consistent with the hypothesis that ITP is a heterogeneous disorder and that some patients have evidence of oligoclonality, whereas other patients have polyclonal autoantibodies.

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“…Interestingly, at least in three ITP patients the reactivity of autoantibodies was completely destroyed by only one amino acid substitution (R139G for two patients, and G44 N for one patient), suggesting that the target epitopes were localized on very restricted region on GPIIb in these three patients [16]. Regarding the epitopes of anti-GPIb/IX autoantibodies, He et al [17] examined their localization by employing short linear fragments of GPIba. They showed that six of 16 anti-GPIb/ IX antibodies in ITP patients recognize a short amino acid sequence (amino acids 333-341) in GPIba.…”

Section: Abnormalities In B Cells: Production Of Anti-platelet Autoanmentioning

confidence: 99%

Pathophysiology and management of primary immune thrombocytopenia

Kashiwagi

Tomiyama

2013

Int J Hematol

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Primary immune thrombocytopenia, or idiopathic thrombocytopenic purpura (ITP), is an autoimmune disorder characterized by isolated thrombocytopenia due to accelerated platelet destruction and impaired platelet production. Autoantibodies against platelet surface glycoproteins, such as GPIIb/IIIa and GPIb/IX complexes, play major roles in both platelet destruction and impaired platelet production, although autoantibody-independent mechanisms, such as T cell-mediated cytotoxicity, may also be involved in its pathogenesis. Recent advances in the localization of autoantigenic epitopes and the characterization of T cell functional abnormalities in ITP patients have improved our understanding of the pathophysiology of this disease. Although corticosteroids and splenectomy remain central to the treatment of ITP, a new class of drugs, i.e., thrombopoietin receptor agonists (TPO-RAs) and rituximab, have substantially broadened the therapeutic options for refractory ITP patients. Moreover, the success of TPO-RAs in ITP patients shows that reduced platelet production caused by impaired megakaryocytopoiesis plays a greater role in ITP than previously recognized.

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Extracellular epitopes of platelet glycoprotein Ib alpha reactive with serum antibodies from patients with chronic idiopathic thrombocytopenic purpura

Cited by 43 publications

References 35 publications

Clonal Restriction of Platelet-associated Anti-GPIIb/IIIa Autoantibodies in Patients with Chronic ITP

Clonal Restriction of Platelet-associated Anti-GPIIb/IIIa Autoantibodies in Patients with Chronic ITP

The IgG subclasses of platelet‐associated autoantibodies directed against platelet glycoproteins IIb/IIIa in patients with idiopathic thrombocytopenic purpura

Pathophysiology and management of primary immune thrombocytopenia

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