The Expression of Immune Checkpoint CD28 rs1980422-related Single-nucleotide Polymorphisms in the Primary Immune Thrombocytopenia

Immune Thrombocytopenia Clinical Trial

Official title:

The Expression of Immune Checkpoint CD28 rs1980422-related Single-nucleotide Polymorphisms in the Primary Immune Thrombocytopenia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05468866
• Other study ID #: Soh-Med-22-07-21
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 1, 2022
• Est. completion date: March 1, 2023

Study information

• Verified date: July 2022
• Source: Sohag University
• Contact: Bedor E Hussien, assistant lecture
• Phone: 01066072377
• Email: bodor.badr[@]med.sohag.edu.eg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary immune thrombocytopenia (ITP), one of the most common bleeding disorders, is characterized by reduced platelet count and an increased risk of bleeding ITP is an acquired autoimmune disease, in which platelets are opsonized by auto-antibodies and destroyed by phagocytic cells ITP pathogenesis involves a hyper-activated T cell response, which is important for cell-mediated cytotoxicity and IgG production Therefore, investigating T cell abnormalities in ITP patients may reveal the mechanism of pathogenesis and development of ITP.

The costimulatory molecules of T cells consist of CD28, inducible costimulatory (ICOS), TNF superfamily member 4 (TNFSF4), and DNAM1 (CD226), and the co-inhibitory molecules contain TIM3, cytotoxic T-lymphocyte associated protein 4 (CTLA4), programmed death-1 (PD1), and lymphocyte activating 3 (LAG3) Among these, CD28 and CTLA4 represent the best-studied costimulatory pathways. CD28 and CTLA4 interact with two ligands (CD80 and CD86) on the surface of antigen-presenting cells (APCs), introducing a positive stimulatory and a negative inhibitory signal into T cells, respectively

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: March 1, 2023
• Est. primary completion date: March 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 65 Years

Eligibility

Inclusion Criteria:

• approval to sign an informed written consent

• patient with newly diagnosed ITP

• platelet count of peripheral blood < 100×109/ L on at least two consecutive routine blood tests, normal or increased megakaryocyte count in bone marrow (as previously diagnosed)

• no other disease or condition related to thrombocytopenia

• patient age > 1 year and < 65 years

Exclusion Criteria:

• Refusal to sign an informed written consent

• Patients with other autoimmune or hemorrhagic diseases (e.g., SLE, severe anemia), or thrombocytopenia due to pregnancy, viruses (e.g., hepatitis C virus, human immunodeficiency virus)

• active infections

• vaccinations, or drugs (e.g., heparin) .

Related Conditions & MeSH terms

• Immune Thrombocytopenia
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia

Intervention

Genetic:
• Genotyping of rs1980422-related single-nucleotide polymorphisms by real time PCR
detection of rs1980422-related single-nucleotide polymorphisms and percentage of (CD3,CD4,CD28) by immunophenotyping

Locations

Country	Name	City	State
Egypt	Sohag University Hospital	Sohag

Sponsors (1)

Lead Sponsor	Collaborator
Sohag University

Country where clinical trial is conducted

Egypt, 

References & Publications (4)

Badami E, Cexus ONF, Quaratino S. Activation-induced cell death of self-reactive regulatory T cells drives autoimmunity. Proc Natl Acad Sci U S A. 2019 Dec 9. pii: 201910281. doi: 10.1073/pnas.1910281116. [Epub ahead of print] — View Citation

Curdy N, Lanvin O, Laurent C, Fournié JJ, Franchini DM. Regulatory Mechanisms of Inhibitory Immune Checkpoint Receptors Expression. Trends Cell Biol. 2019 Oct;29(10):777-790. doi: 10.1016/j.tcb.2019.07.002. Epub 2019 Aug 1. Review. — View Citation

Ferreira RC, Castro Dopico X, Oliveira JJ, Rainbow DB, Yang JH, Trzupek D, Todd SA, McNeill M, Steri M, Orrù V, Fiorillo E, Crouch DJM, Pekalski ML, Cucca F, Tree TI, Vyse TJ, Wicker LS, Todd JA. Chronic Immune Activation in Systemic Lupus Erythematosus and the Autoimmune PTPN22 Trp(620) Risk Allele Drive the Expansion of FOXP3(+) Regulatory T Cells and PD-1 Expression. Front Immunol. 2019 Nov 8;10:2606. doi: 10.3389/fimmu.2019.02606. eCollection 2019. — View Citation

Huang C, Zhu HX, Yao Y, Bian ZH, Zheng YJ, Li L, Moutsopoulos HM, Gershwin ME, Lian ZX. Immune checkpoint molecules. Possible future therapeutic implications in autoimmune diseases. J Autoimmun. 2019 Nov;104:102333. doi: 10.1016/j.jaut.2019.102333. Epub 2019 Sep 26. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	rs1980422-related single-nucleotide polymorphisms	Genotyping of rs1980422-related single-nucleotide polymorphisms by real time PCR.	6 months