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

NCT ID: NCT05468866

Last Updated: 2022-07-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-01

Study Completion Date

2023-03-01

Brief Summary

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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

Detailed Description

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Conditions

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Immune Thrombocytopenia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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group (I)

Group (I): represents the healthy control individuals (30 person) (recruited from the blood donors at the blood bank)

Group Type ACTIVE_COMPARATOR

Genotyping of rs1980422-related single-nucleotide polymorphisms by real time PCR

Intervention Type GENETIC

detection of rs1980422-related single-nucleotide polymorphisms and percentage of (CD3,CD4,CD28) by immunophenotyping

Group (II)

Group (II): represents the cases of immune thrombocytopenia (70 cases).

Group Type ACTIVE_COMPARATOR

Genotyping of rs1980422-related single-nucleotide polymorphisms by real time PCR

Intervention Type GENETIC

detection of rs1980422-related single-nucleotide polymorphisms and percentage of (CD3,CD4,CD28) by immunophenotyping

Interventions

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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

Intervention Type GENETIC

Other Intervention Names

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Immunophenotyping (CD3, CD4, CD28) by flow cytometry

Eligibility Criteria

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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) .
Minimum Eligible Age

1 Year

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sohag University

OTHER

Sponsor Role lead

Responsible Party

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Bedor Elsayed Hussien

Assistant lecturer of clinical and chemical pathology

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Sohag University Hospital

Sohag, , Egypt

Site Status

Countries

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Egypt

Central Contacts

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Bedor E Hussien, assistant lecture

Role: CONTACT

01066072377

Ahmed A Allam, assistant professor

Role: CONTACT

Facility Contacts

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Osama R ELsheref, professor

Role: primary

References

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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 26;116(52):26788-26797. doi: 10.1073/pnas.1910281116. Epub 2019 Dec 9.

Reference Type BACKGROUND
PMID: 31818938 (View on PubMed)

Curdy N, Lanvin O, Laurent C, Fournie 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.

Reference Type BACKGROUND
PMID: 31378317 (View on PubMed)

Ferreira RC, Castro Dopico X, Oliveira JJ, Rainbow DB, Yang JH, Trzupek D, Todd SA, McNeill M, Steri M, Orru 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 Trp620 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.

Reference Type BACKGROUND
PMID: 31781109 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31564474 (View on PubMed)

Other Identifiers

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Soh-Med-22-07-21

Identifier Type: -

Identifier Source: org_study_id

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