Autoreactive T cells to platelet GPIIb-IIIa in immune thrombocytopenic purpura. Role in production of anti-platelet autoantibody.

Kuwana, Masataka; Kaburaki, Junichi; Ikeda, Yasuo

doi:10.1172/jci4238

Cited by 213 publications

(186 citation statements)

References 43 publications

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“…However, Tcell mediated mechanisms independent from autoantibodies may also be involved (5). The presence of auto-reactive T cell clones against GPIIb/IIIa epitopes in patients with ITP were shown by Kuwana et al (19). Other studies have also shown the presence of cytotoxic T cells against autologous thrombocytes.…”

Section: Discussionmentioning

confidence: 94%

Seasonal Association of Immune Thrombocytopenia in Adults

Tombak¹,

Boztepe²,

Tiftik³

et al. 2015

Balkan Med J

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Background:Immune thrombocytopenia (ITP) is an autoimmune disorder. It is characterized by thrombocytopenia due to thrombocyte destruction mediated by autoantibodies; however, cytotoxic and defective regulatory T-lymphocytes play an important role in its pathogenesis. While childhood ITP is usually acute, self-limiting and generally seasonal in nature, ITP in adults is usually chronic; its relation with seasons has not been studied. Aims: We investigated whether months and/or seasons have triggering roles in adults with ITP. Study Design: Descriptive study. Methods: A retrospective case review of adult patients with primary ITP diagnosed at various University Hospitals in cities where Mediterranean climate is seen was performed. Demographic data, date of referral and treatments were recorded. Corticosteroid-resistant, chronic and refractory cases were determined. Relation between sex, corticosteroid-resistant, chronic and refractory ITP with the seasons was also investigated. Results: The study included 165 patients (124 female, mean age=42.8±16.6). Most cases of primary ITP were diagnosed in the spring (p=0.015). Rates of patients diagnosed according to the seasons were as follows: 35.8% in spring, 23% in summer, 20.6% in fall, and 20.6% in winter. With respect to months, the majority of cases occurred in May (18.2%). Time of diagnosis according to the seasons did not differ between genders (p=0.699). First-line treatment was corticosteroids in 97.3%, but 35% of the cases were corticosteroid-resistant. Steroid-resistant patients were mostly diagnosed in the spring (52.1%) (p=0.001). ITP was chronic in 52.7% of the patients and they were also diagnosed mostly in the spring (62.7%) (p=0.149). Conclusion: This is the first study showing seasonal association of ITP in adults and we have observed that ITP in adults is mostly diagnosed in the spring. The reason why more patients are diagnosed in the spring may be due to the existence of atmospheric pollens reaching maximum levels in the spring in places where a Mediterranean climate is seen.

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Section: Discussionmentioning

confidence: 94%

Seasonal Association of Immune Thrombocytopenia in Adults

Tombak¹,

Boztepe²,

Tiftik³

et al. 2015

Balkan Med J

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“…This might be expected, as B cells are the ultimate producers of anti-platelet antibodies, and patients with ITP have an increased generation of antiplatelet antibodies [23]. The pathogenic B cells are stimulated by platelet-specific helper T cells to proliferate into autoantibody-secreting cells and thus they may be responsible for decreased peripheral blood platelet count in patients with ITP [24]. Rituximab, an anti-CD20 monoclonal antibody that depletes B cells, has been used to treat ITP for about a decade and has shown its efficacy in a subpopulation of ITP patients [25,26].…”

Section: Discussionmentioning

confidence: 99%

Regulatory and Memory B Lymphocytes in Children With Newly Diagnosed Immune Thrombocytopenia

Zahran¹,

Aly²,

Elabd³

et al. 2017

J Hematol

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Background: Immune (idiopathic) thrombocytopenic purpura (ITP) is a primary autoimmune disease. It is characterized by a diminished peripheral platelet count (< 100 × 10 9 /L) caused by platelet destruction with an increased risk of mucocutaneous bleeding. The diagnosis of ITP depends on clinical characteristics and the laboratory examinations conducted, as well as the ability to exclude other diseases associated with thrombocytopenia. Antiplatelet autoantibodies are responsible for platelet destruction and probably for inhibition of megakaryopoiesis. B lymphocytes participate in immune responses through production of antibodies, antigen presentation to T cells, and cytokine secretion. The aims of this study were to investigate the levels of Bregs and memory B lymphocytes in newly diagnosed pediatric ITP patients and to correlate their levels with the course of the disease.

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“…Support for the primary role of T cells in promoting specific autoantibody responses comes from work in other diseases such as scleroderma, systemic lupus erythematosus, anti-phospholipid Ab syndrome, and immune thrombocytopenic purpura (12)(13)(14)(15)(16)(17). Moreover, in the T cell-mediated autoimmune disease primary biliary cirrhosis, bile duct-infiltrating T cells and a subpopulation of peripheral blood CD4 ϩ T cells recognize the same Ag (pyruvate dehydrogenase complex) that is targeted by a highly stereotypical, but nonpathogenic, Ab response (18 -21).…”

Section: P Olymyositis (Pm)mentioning

confidence: 99%

Critical Requirement for Professional APCs in Eliciting T Cell Responses to Novel Fragments of Histidyl-tRNA Synthetase (Jo-1) in Jo-1 Antibody-Positive Polymyositis

Ascherman

Oriss

Oddis

et al. 2002

The Journal of Immunology

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Polymyositis (PM) is an autoimmune muscle disease characterized by oligoclonal T cell infiltrates mediating myocytotoxicity. Although antigenic triggers for this process remain undefined, clinically homogeneous subsets of PM patients are characterized by autoantibodies directed against nuclear and cytoplasmic Ags that include histidyl-tRNA synthetase (Jo-1). Available evidence suggests that formation of anti-Jo-1 autoantibodies is Ag-driven and therefore dependent on CD4+ T cells that may also direct cytolytic CD8+ T cells involved in myocyte destruction. To assess peripheral blood T cell responses to Jo-1, we first subcloned full-length human Jo-1 as well as novel fragments of Jo-1 into the maltose-binding protein expression vector pMALc2. Expressed proteins were then used in standard proliferation assays with either PBMC or autologous DCs as sources of APCs. Although PBMC-derived APCs and DCs both supported peripheral blood T cell proliferation when primed with full-length human Jo-1, only DCs promoted proliferative responses to a unique amino-terminal fragment of Jo-1. mAb blockade of different HLA Ags revealed that these responses were MHC class II dependent. Therefore, for the first time, these studies demonstrate anti-Jo-1 T cell responses in Jo-1 Ab-positive PM patients as well as in healthy control subjects. More importantly, this work underscores the critical importance of APC type in dictating T cell responses to a novel antigenic fragment of Jo-1.

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Autoreactive T cells to platelet GPIIb-IIIa in immune thrombocytopenic purpura. Role in production of anti-platelet autoantibody.

Cited by 213 publications

References 43 publications

Seasonal Association of Immune Thrombocytopenia in Adults

Seasonal Association of Immune Thrombocytopenia in Adults

Regulatory and Memory B Lymphocytes in Children With Newly Diagnosed Immune Thrombocytopenia

Critical Requirement for Professional APCs in Eliciting T Cell Responses to Novel Fragments of Histidyl-tRNA Synthetase (Jo-1) in Jo-1 Antibody-Positive Polymyositis

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