Clinical trial NCT05410249: Assessment of FOXP3 Gene Polymorphisms and Serum Interleukin 10 in Patients With ITP
Official title: Assessment of FOXP3 Gene Polymorphisms and Serum Interleukin 10 and Their Clinical Significance in Adult Patients With Immune Thrombocytopenia
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Thrombocytopenia
Keywords: polymorphism
FOXp3
serum IL10
Lead sponsor: Sohag University
Sponsor class: OTHER
First posted: 2022-06-08
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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

Brief summary: 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 \[7, 8\].

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.

Eligibility criteria: 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

Primary outcomes:
measure: SNP effect in FOXP3 gene in patients ITP
timeFrame: 26 May to August 2022
measure: Association of serum IL-10 levels in both groups( patients with ITP and normal control)
timeFrame: 26 May to August 2022
measure: Association of SNP in FOXP3 gene and the clinical presentation in adult patients with ITP
timeFrame: 26 May to August 2022
Secondary outcomes:
Other outcomes:
Locations:
city: Sohag
country: Egypt
facility: Faculty Of Medicine
Study officials:
affiliation: faculty of medicine, Sohag university
name: Asmaa A Abdelbaset, lecturer
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.