Immune Markers in Pediatric ITP
Study Details
Study Description
Brief Summary
Immune thrombocytopenia (ITP) is a common autoimmune disease characterized by low platelet count and increased risk of bleeding. It affects approximately 50 to 100 cases per million people per year, with children accounting for half of the cases.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
Antiplatelet factors in the plasma of ITP patients, specifically IgG, have been attributed to platelet destruction through phagocytosis or complement-mediated lysis. However, these antibodies are only present in 60-70% of ITP patients, suggesting that other mechanisms may be involved in platelet destruction.
B lymphocytes play a critical role in immune responses through antibody production, antigen presentation to T cells, and cytokine secretion. CD4+ T helper cells play a crucial role in supporting B cell development into antibody-secreting plasma cells. Furthermore, evidence of auto reactive CD4+ T cells targeting platelet epitopes has been reported.
It was found that there is clonal expansion of a particular subset of CD8+ T cells, known as terminally differentiated effector memory T cells (TEMRA cells), in refractory ITP. Furthermore, CD8+ T cells induce platelet activation and apoptosis in an antibody-independent mechanism for refractory thrombocytopenia that may be amenable to therapeutic targeting. IFN-γ is an important cytokine involved in host defence and immune regulation. It is primarily produced by T helper, cytotoxic T, and natural killer cells. Dysregulated secretion of IFN-γ has been implicated in the development of autoimmune disorders. Initial studies on ITP focused on the role of autoantibodies. Therefore, drug discovery efforts have focused on suppressing aberrant humoral immunity through B cell depletion, disruption of immunoreceptor, and inhibition of autoantibody activity. By comparing the marker expression in different treatment response groups, we can potentially identify markers that may serve as predictive or prognostic indicators of treatment response. This information could be valuable for guiding treatment decisions and optimizing patient outcomes in pediatric ITP.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Respondents to second-line therapy
|
Diagnostic Test: complete blood count, CD3+ , CD4+ , CD8+, CD16+, CD56+, IFN-γ.
Full history
Thorough clinical examinations
Laboratory investigations will include:
complete blood count with focus on platelet count, platelet distribution width and mean platelet volume. Platelet count will be confirmed by direct blood film and blood smear.
Measurements of CD3+, CD4+, CD8+ and natural killer cells (CD16+, CD56+) will be conducted using flow cytometry.
Serum IFN-γ levels will be determined using an ELISA kit.
Response to the treatment will be assessed according to The International Working Group criteria which defines Response as platelet count ≥ 30 x 10⁹/L and >2-fold increase in platelet count from baseline and absence of bleeding, measured on 2 occasions greater than 7 days apart. No response is characterized by a platelet count <30 x 10⁹/L or a less than 2-fold increase in platelet count from baseline, or the presence of bleeding.
|
| Non-Respondents to second-line therapy
|
Diagnostic Test: complete blood count, CD3+ , CD4+ , CD8+, CD16+, CD56+, IFN-γ.
Full history
Thorough clinical examinations
Laboratory investigations will include:
complete blood count with focus on platelet count, platelet distribution width and mean platelet volume. Platelet count will be confirmed by direct blood film and blood smear.
Measurements of CD3+, CD4+, CD8+ and natural killer cells (CD16+, CD56+) will be conducted using flow cytometry.
Serum IFN-γ levels will be determined using an ELISA kit.
Response to the treatment will be assessed according to The International Working Group criteria which defines Response as platelet count ≥ 30 x 10⁹/L and >2-fold increase in platelet count from baseline and absence of bleeding, measured on 2 occasions greater than 7 days apart. No response is characterized by a platelet count <30 x 10⁹/L or a less than 2-fold increase in platelet count from baseline, or the presence of bleeding.
|
Outcome Measures
Primary Outcome Measures
- Correlation analysis [One year]
Analysis of the correlation between specific markers expression and treatment response in pediatric patients with immune thrombocytopenia who are receiving second line therapy.
Secondary Outcome Measures
- Assessment of treatment response [One year]
Assessment of response to second line therapy (eltrombopag, romiplostim) in pediatric patients with immune thrombocytopenic purpura using clinical and laboratory findings.
Eligibility Criteria
Criteria
Inclusion Criteria:
- Pediatric patients diagnosed with immune thrombocytopenia who are undergoing second line therapy with either eltrombopag or romiplostim.
Exclusion Criteria:
- Include acute immune thrombocytopenic children receiving first line therapy and those with secondary immune thrombocytopenia.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Assiut University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
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- Malik A, Sayed AA, Han P, Tan MMH, Watt E, Constantinescu-Bercu A, Cocker ATH, Khoder A, Saputil RC, Thorley E, Teklemichael A, Ding Y, Hart ACJ, Zhang H, Mitchell WA, Imami N, Crawley JTB, Salles-Crawley II, Bussel JB, Zehnder JL, Adams S, Zhang BM, Cooper N. The role of CD8+ T-cell clones in immune thrombocytopenia. Blood. 2023 May 18;141(20):2417-2429. doi: 10.1182/blood.2022018380.
- Newland AC, Sanchez-Gonzalez B, Rejto L, Egyed M, Romanyuk N, Godar M, Verschueren K, Gandini D, Ulrichts P, Beauchamp J, Dreier T, Ward ES, Michel M, Liebman HA, de Haard H, Leupin N, Kuter DJ. Phase 2 study of efgartigimod, a novel FcRn antagonist, in adult patients with primary immune thrombocytopenia. Am J Hematol. 2020 Feb;95(2):178-187. doi: 10.1002/ajh.25680. Epub 2019 Dec 10.
- Pollard KM, Cauvi DM, Toomey CB, Morris KV, Kono DH. Interferon-gamma and systemic autoimmunity. Discov Med. 2013 Sep;16(87):123-31.
- Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, Bussel JB, Cines DB, Chong BH, Cooper N, Godeau B, Lechner K, Mazzucconi MG, McMillan R, Sanz MA, Imbach P, Blanchette V, Kuhne T, Ruggeri M, George JN. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009 Mar 12;113(11):2386-93. doi: 10.1182/blood-2008-07-162503. Epub 2008 Nov 12.
- Shulman NR, Marder VJ, Weinrach RS. Similarities between known antiplatelet antibodies and the factor responsible for thrombocytopenia in idiopathic purpura. Physiologic, serologic and isotopic studies. Ann N Y Acad Sci. 1965 Jun 30;124(2):499-542. doi: 10.1111/j.1749-6632.1965.tb18984.x. No abstract available.
- van Leeuwen EF, van der Ven JT, Engelfriet CP, von dem Borne AE. Specificity of autoantibodies in autoimmune thrombocytopenia. Blood. 1982 Jan;59(1):23-6.
- Zufferey A, Kapur R, Semple JW. Pathogenesis and Therapeutic Mechanisms in Immune Thrombocytopenia (ITP). J Clin Med. 2017 Feb 9;6(2):16. doi: 10.3390/jcm6020016.
- ITPIMMUNEMARKERS