{"title":"聚焦主题议题:免疫性血小板减少症(ITP)","authors":"J. Semple, R. Kapur","doi":"10.21037/AOB-2021-01","DOIUrl":null,"url":null,"abstract":"Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder mediated by anti-platelet autoantibodies and antigen-specific T cells (1,2). These immune effectors either destroy platelets peripherally in the spleen and/or impair platelet production in the bone marrow. The most recent pathophysiologic studies have shown that abnormal T cell responses, particularly, defective T regulatory cell (Treg) activity are central to the autoimmune pathogenesis of ITP and various therapeutics can restore these responses. Just in the last 2 years, for example, there is a significant literature on ITP pathophysiology and it points to the concept that the disease is initiated by flawed self-tolerance mechanisms (1). It appears that understanding how to specifically modulate T cells in patients with ITP will undoubtedly lead to effective antigen-specific therapeutics. This issue of AOB will be dedicated to ITP with a series of manuscripts written by leading experts in the field of ITP management and treatment. It now appears that a great deal of new treatments are available for the disease, and we now have a better understanding of how these new treatments may increase platelet counts in ITP. In the first chapter, Branch (3) and colleagues re-visit what is known about the efficacy and mechanism of action of intravenous immunoglobulin (IVIg) treatment for ITP in adults. IVIg has been used for almost 40 years as a therapeutic for the treatment of ITP and was originally found to be an efficacious treatment for pediatric ITP and later for adults suffering from the disorder. The chapter delves into the success of IVIg treatment over the years and highlights its use with other therapeutics. It points out that despite its many years of use, the mechanism of action of IVIg in ITP still remains controversial with many experimentally-supported theories as to its mechanism of action. Even so, the authors suggest that IVIg will likely continue to be a first-line therapy for adult ITP, particularly when patients suffer from bleeding symptoms. In the second chapter Schmidt (4) and colleagues discuss IVIg usage in pediatric patients with ITP. In childhood ITP, morbidity is significant due to the risk of bleeding and there is a reduced health-related quality of life (HRQoL). The authors suggest that IVIg treatment accelerates the remission of thrombocytopenia in newly diagnosed ITP and reduces bleeding symptoms, but there are disadvantages such as side effects and costs. They discuss their recent randomized controlled study (TIKI) that showed that IVIg does not affect the development of chronic ITP. It appears that approximately 60% of children with newly diagnosed ITP have a sustained response to IVIg and this response is associated with long-term remission. They then move into recent molecular and clinical data, which shows that treatment responders can be identified before IVIg administration and this is associated with a transient, self-limiting ITP disease course. They conclude by suggesting that the development of clinical and molecular prediction scores could allow for individualized treatment decisions and to design studies aimed at identifying children who benefit from adjunctive or alternative treatments. trials pertaining to the primary and secondary management of primary ITP with a focus on novel agents. They discuss very recent (within 2 years) literature pertaining to articles discussing therapies other than the TPO-RAs or pediatric ITP treatments. They have collated evidence on corticosteroids and IVIG which remain the mainstay of first line management. With respect to second line treatments, in which rituximab and splenectomy were the prominent players, they discuss these and the new therapeutics including the Syk inhibitors, FcRn agonists, MMF and daratumumab.","PeriodicalId":72211,"journal":{"name":"Annals of blood","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Focused themed issue on immune thrombocytopenia (ITP)\",\"authors\":\"J. Semple, R. Kapur\",\"doi\":\"10.21037/AOB-2021-01\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder mediated by anti-platelet autoantibodies and antigen-specific T cells (1,2). These immune effectors either destroy platelets peripherally in the spleen and/or impair platelet production in the bone marrow. The most recent pathophysiologic studies have shown that abnormal T cell responses, particularly, defective T regulatory cell (Treg) activity are central to the autoimmune pathogenesis of ITP and various therapeutics can restore these responses. Just in the last 2 years, for example, there is a significant literature on ITP pathophysiology and it points to the concept that the disease is initiated by flawed self-tolerance mechanisms (1). It appears that understanding how to specifically modulate T cells in patients with ITP will undoubtedly lead to effective antigen-specific therapeutics. This issue of AOB will be dedicated to ITP with a series of manuscripts written by leading experts in the field of ITP management and treatment. It now appears that a great deal of new treatments are available for the disease, and we now have a better understanding of how these new treatments may increase platelet counts in ITP. In the first chapter, Branch (3) and colleagues re-visit what is known about the efficacy and mechanism of action of intravenous immunoglobulin (IVIg) treatment for ITP in adults. IVIg has been used for almost 40 years as a therapeutic for the treatment of ITP and was originally found to be an efficacious treatment for pediatric ITP and later for adults suffering from the disorder. The chapter delves into the success of IVIg treatment over the years and highlights its use with other therapeutics. It points out that despite its many years of use, the mechanism of action of IVIg in ITP still remains controversial with many experimentally-supported theories as to its mechanism of action. Even so, the authors suggest that IVIg will likely continue to be a first-line therapy for adult ITP, particularly when patients suffer from bleeding symptoms. In the second chapter Schmidt (4) and colleagues discuss IVIg usage in pediatric patients with ITP. In childhood ITP, morbidity is significant due to the risk of bleeding and there is a reduced health-related quality of life (HRQoL). The authors suggest that IVIg treatment accelerates the remission of thrombocytopenia in newly diagnosed ITP and reduces bleeding symptoms, but there are disadvantages such as side effects and costs. They discuss their recent randomized controlled study (TIKI) that showed that IVIg does not affect the development of chronic ITP. It appears that approximately 60% of children with newly diagnosed ITP have a sustained response to IVIg and this response is associated with long-term remission. They then move into recent molecular and clinical data, which shows that treatment responders can be identified before IVIg administration and this is associated with a transient, self-limiting ITP disease course. They conclude by suggesting that the development of clinical and molecular prediction scores could allow for individualized treatment decisions and to design studies aimed at identifying children who benefit from adjunctive or alternative treatments. trials pertaining to the primary and secondary management of primary ITP with a focus on novel agents. They discuss very recent (within 2 years) literature pertaining to articles discussing therapies other than the TPO-RAs or pediatric ITP treatments. They have collated evidence on corticosteroids and IVIG which remain the mainstay of first line management. With respect to second line treatments, in which rituximab and splenectomy were the prominent players, they discuss these and the new therapeutics including the Syk inhibitors, FcRn agonists, MMF and daratumumab.\",\"PeriodicalId\":72211,\"journal\":{\"name\":\"Annals of blood\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2021-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of blood\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.21037/AOB-2021-01\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of blood","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.21037/AOB-2021-01","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Focused themed issue on immune thrombocytopenia (ITP)
Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder mediated by anti-platelet autoantibodies and antigen-specific T cells (1,2). These immune effectors either destroy platelets peripherally in the spleen and/or impair platelet production in the bone marrow. The most recent pathophysiologic studies have shown that abnormal T cell responses, particularly, defective T regulatory cell (Treg) activity are central to the autoimmune pathogenesis of ITP and various therapeutics can restore these responses. Just in the last 2 years, for example, there is a significant literature on ITP pathophysiology and it points to the concept that the disease is initiated by flawed self-tolerance mechanisms (1). It appears that understanding how to specifically modulate T cells in patients with ITP will undoubtedly lead to effective antigen-specific therapeutics. This issue of AOB will be dedicated to ITP with a series of manuscripts written by leading experts in the field of ITP management and treatment. It now appears that a great deal of new treatments are available for the disease, and we now have a better understanding of how these new treatments may increase platelet counts in ITP. In the first chapter, Branch (3) and colleagues re-visit what is known about the efficacy and mechanism of action of intravenous immunoglobulin (IVIg) treatment for ITP in adults. IVIg has been used for almost 40 years as a therapeutic for the treatment of ITP and was originally found to be an efficacious treatment for pediatric ITP and later for adults suffering from the disorder. The chapter delves into the success of IVIg treatment over the years and highlights its use with other therapeutics. It points out that despite its many years of use, the mechanism of action of IVIg in ITP still remains controversial with many experimentally-supported theories as to its mechanism of action. Even so, the authors suggest that IVIg will likely continue to be a first-line therapy for adult ITP, particularly when patients suffer from bleeding symptoms. In the second chapter Schmidt (4) and colleagues discuss IVIg usage in pediatric patients with ITP. In childhood ITP, morbidity is significant due to the risk of bleeding and there is a reduced health-related quality of life (HRQoL). The authors suggest that IVIg treatment accelerates the remission of thrombocytopenia in newly diagnosed ITP and reduces bleeding symptoms, but there are disadvantages such as side effects and costs. They discuss their recent randomized controlled study (TIKI) that showed that IVIg does not affect the development of chronic ITP. It appears that approximately 60% of children with newly diagnosed ITP have a sustained response to IVIg and this response is associated with long-term remission. They then move into recent molecular and clinical data, which shows that treatment responders can be identified before IVIg administration and this is associated with a transient, self-limiting ITP disease course. They conclude by suggesting that the development of clinical and molecular prediction scores could allow for individualized treatment decisions and to design studies aimed at identifying children who benefit from adjunctive or alternative treatments. trials pertaining to the primary and secondary management of primary ITP with a focus on novel agents. They discuss very recent (within 2 years) literature pertaining to articles discussing therapies other than the TPO-RAs or pediatric ITP treatments. They have collated evidence on corticosteroids and IVIG which remain the mainstay of first line management. With respect to second line treatments, in which rituximab and splenectomy were the prominent players, they discuss these and the new therapeutics including the Syk inhibitors, FcRn agonists, MMF and daratumumab.