Assessment of FOXP3 Gene Polymorphisms and Serum Interleukin 10 in Patients With ITP (FoxP3ITP)

Assessment of FOXP3 Gene Polymorphisms and Serum Interleukin 10 and Their Clinical Significance in Adult Patients With Immune Thrombocytopenia

Immune thrombocytopenia (ITP) is an autoimmune condition characterized by increased platelet destruction and suppression of production resulting in isolated thrombocytopenia. The exact etiology of ITP is unknown; however, multiple disease mechanisms exist and are mostly related to immune dysregulation [1].

Many studies in recent years have indicated that regulatory T cells (Tregs) play a critical role in the maintenance of immunological tolerance, and they have been reported to be defective in ITP patients, either numerically or functionally. [2-6]. They inhibit the activation and proliferation of effector T cells by the secretion of cytokines such as interleukin-10 (IL-10) and tumor growth factor-β (TGF-β) and by cell-to-cell interaction [7, 8].

Study Overview

• Status: Recruiting
• Conditions: Thrombocytopenia
• Intervention / Treatment: Diagnostic test: Serum IL10 By ELISA; Diagnostic test: SNP -3279 A/C of FOXP3; Diagnostic test: SNP-924 A/G Of FOXP3

Detailed Description

The suppressor function of Treg cells may be compromised if the FOXP3 gene is deficient. FOXP3 gene single nucleotide polymorphisms (SNPs), particularly regulatory polymorphisms in the promoter regions, have been linked to a variety of autoimmune diseases, including allergic rhinitis, type I diabetes (TID), systemic lupus erythematosus (SLE), multiple sclerosis (MS), and autoimmune thyroid diseases (AITD), according to numerous studies [9-13].

The FOXP3 gene's promoter region, which is crucial in gene expression and Treg activation, may contain important SNPs. The 6054 del/ATT and 924A > G SNPs are functionally well-defined and are distinguished by the relevance of studies on them among these SNPs. [14, 15].

The Interleukin 10 (IL-10) cytokine is required for regulating immune functions by promoting the widespread suppression of immune responses through its pleiotropic effects. IL-10 secretion from CD4+CD25+FoxP3+ regulatory cells (Tregs), macrophages and other leukocytes followed by subsequent binding to IL-10 receptors on macrophages and dendritic cells (DCs) has been linked to reduced antigen presentation and increased T-cell anergy [16]. The relationship between the two FOXP3 polymorphisms and ITP has not been well elucidated, hence the objective of this study is to explore if these functional polymorphisms are linked to ITP, how they correlate to IL-10 levels, and how they relate to other features of clinical presentation in adult patients with ITP.

• Study Type: Observational
• Enrollment (Anticipated): 130

Contacts and Locations

• Study Contact: Name: Noha S Shafik, Lecturer; Phone Number: 01067261504; Email: nohasaber@med.sohag.edu.eg
• Study Contact Backup: Name: Mahmoud G Mahmoud, Lecturer; Email: mahmoudgaber@med.sohag.edu.eg

Study Locations

• Egypt
  • Sohag, Egypt, 82524
    • Recruiting
    • Faculty of Medicine
    • Contact: Mahmoud G Mahmoud, Lecturer; Email: mahmoudgaber@med.sohag.edu.eg
    • Contact: Noha S Shafik, Lecturer; Phone Number: 00201067261504; Email: nohasaber@med.sohag.edu.eg
    • Principal Investigator: Asmaa Baset, Lecturer
    • Principal Investigator: Moustafa A Younis, Lecturer
    • Principal Investigator: Alshimaa H Abdelall, Lecturer
    • Principal Investigator: Mahmoud Ibrahim, lecturer

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Patients with primary ITP and aged 18 and older will be included in the study. Patients under 18 and those with proven secondary ITP [as cases initiated by or associated with infections due to human immunodeficiency virus (HIV-associated), hepatitis B virus, or hepatitis C virus-associated secondary ITP] will be excluded. Moreover, patients with accompanying autoimmune disorders such as systemic lupus erythematosus (SLE) and patients of malignancies were excluded.

All patients will be subjected to a thorough assessment of history, complete clinical examination, and investigations

Description

Inclusion Criteria:

• Patients with primary ITP and aged 18 and older will be included in the study.

Exclusion Criteria:

1. Patients under 18 and those with proven secondary ITP [as cases initiated by or associated with infections due to human immunodeficiency virus (HIV-associated), hepatitis B virus, or hepatitis C virus-associated secondary ITP] .
2. Patients with accompanying autoimmune disorders such as systemic lupus erythematosus (SLE).
3. Patients with malignancies will be excluded

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with primary ITP; Patients with primary ITP and aged 18 and older will be included in the study. Patients under 18 and those with proven secondary ITP [as cases initiated by or associated with infections due to human immunodeficiency virus (HIV-associated), hepatitis B virus, or hepatitis C virus-associated secondary ITP] will be excluded. Moreover, patients with accompanying autoimmune disorders such as systemic lupus erythematosus (SLE) and patients of malignancies were excluded.	Diagnostic test: Serum IL10 By ELISA; measurement Of IL10 by ELISA; Diagnostic test: SNP -3279 A/C of FOXP3; Genotyping of -6054 del/ATT will be performed using the real-time polymerase chain reaction.; Diagnostic test: SNP-924 A/G Of FOXP3; Genotyping of -924 A/G polymorphisms was performed using the real-time polymerase chain reaction.
normal individuals; The control group will be age-matched and sex-matched normal healthy volunteers.	Diagnostic test: Serum IL10 By ELISA; measurement Of IL10 by ELISA; Diagnostic test: SNP -3279 A/C of FOXP3; Genotyping of -6054 del/ATT will be performed using the real-time polymerase chain reaction.; Diagnostic test: SNP-924 A/G Of FOXP3; Genotyping of -924 A/G polymorphisms was performed using the real-time polymerase chain reaction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SNP effect in FOXP3 gene in patients ITP	different genotypes of FOXP3 in patients with ITP will be determined using real time PCR	26 May to August 2022
Association of serum IL-10 levels in both groups( patients with ITP and normal control)	measurement of serum IL10 in patients with ITP and normal controls using ELISA	26 May to August 2022
Association of SNP in FOXP3 gene and the clinical presentation in adult patients with ITP	evaluation and statistical analysis of effect of SNP in FOXP3 in the clinical picture in adult patients with ITP	26 May to August 2022

Collaborators and Investigators

• Sponsor: Sohag University
• Investigators: Principal Investigator: Asmaa A Abdelbaset, lecturer, Faculty of Medicine, Sohag University

Publications and helpful links

General Publications

• Ballantine LE, Ong J, Midgley A, Watson L, Flanagan BF, Beresford MW. The pro-inflammatory potential of T cells in juvenile-onset systemic lupus erythematosus. Pediatr Rheumatol Online J. 2014 Jan 16;12:4. doi: 10.1186/1546-0096-12-4.

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2022
• Primary Completion (Actual): December 26, 2022
• Study Completion (Anticipated): September 30, 2023

Study Registration Dates

• First Submitted: May 27, 2022
• First Submitted That Met QC Criteria: June 6, 2022
• First Posted (Actual): June 8, 2022

Study Record Updates

• Last Update Posted (Actual): April 12, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: polymorphism; FOXp3; serum IL10
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Platelet Disorders; Thrombocytopenia
• Other Study ID Numbers: Soh-Med-22-4-34

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No