Viewing Study NCT05570513



Ignite Creation Date: 2024-05-06 @ 6:12 PM
Last Modification Date: 2024-10-26 @ 2:43 PM
Study NCT ID: NCT05570513
Status: NOT_YET_RECRUITING
Last Update Posted: 2022-10-06
First Post: 2022-09-27

Brief Title: Relation of IL23R and IL17A Gene Polymorphisms Plus Serum Levels of IL23 and IL17A to Rheumatoid Arthritis Susceptibility and Activity
Sponsor: Assiut University
Organization: Assiut University

Study Overview

Official Title: Relation of IL23R and IL17A Gene Polymorphisms Plus Serum Levels of IL23 and IL17A to Rheumatoid Arthritis Susceptibility and Activity
Status: NOT_YET_RECRUITING
Status Verified Date: 2022-09
Last Known Status: None
Delayed Posting: No
If Stopped, Why?: Not Stopped
Has Expanded Access: False
If Expanded Access, NCT#: N/A
Has Expanded Access, NCT# Status: N/A
Acronym: None
Brief Summary: Assess the impact of rs2201841 and rs2275913 single nucleotide polymorphism of host genes IL-23R and IL-17A respectively on susceptibility of rheumatoid arthritis

Determine serum levels of IL-23 and IL-17A using ELISA test to investigate their correlation to rheumatoid arthritis disease activity

Compare the 4 biomarkers IL-23R and IL-17A genetic polymorphism and levels of IL-23 and IL-17A as predictors of rheumatoid arthritis susceptibility and disease activity
Detailed Description: Rheumatoid arthritis an autoimmune disease that is associated with progressive disability systemic complications and socioeconomic costs RA affects 05-1 of the human population making it one of the most common autoimmune disorders The incidence of RA increases with age affecting about 6 of the population over 65 years old Women are more affected than men in a ratio of 31 1

The synovitis in RA is characterized by massive cellular infiltration of the synovium consisting mainly of leukocytes such as T and B cells macrophages granulocytes and dendritic cells together with the increased local production of proinflammatory cytokines and chemokines eventually leading to the destruction of the joint and bone 2

Th-17 starts producing IL-17 and IL-22 which in turn stimulate fibroblast-like synoviocytes FLS to secrete IL-8 IL-6 CCL20 and CXCL8 causing inflammation while the macrophages secreted TNF-α results in IL-23 production from FLS forming a positive feedback loop that maintains the production of IL-17 and IL-22 from Th-17 3 Both IL-17 and IL-22 are able to induce osteoclast differentiation from osteoclast progenitor either directly or by elevating Receptor activator of nuclear factor kappa-B ligand RANKL on CD4 and Th-17 which upon ligation with the RANK receptor on osteoclast progenitor stimulates osteoclast differentiation Osteoclasts are a main cause of bone erosion 4

However advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics with improved outcomes 5 Overall current treatment strategies for RA tend to involve targeting pro-inflammatory cytokines and thereby the activation process of inflammation rather than functioning to boost pathways that orchestrate the suppression and resolution of inflammation 6

IL-23 is a pro-inflammatory cytokine that belongs to the IL-12 family together with IL-12 IL-27 IL-35 and IL-39 7 Its actions are mainly mediated by the CD4 T helper subset Th17 a distinct subpopulation of gammadelta T cells Tγδ17 cells subsets of natural killer T NKT cells and type 3 innate lymphoid cells ILC3s 8 The main role of IL-23 is to induce the differentiation of αβ T CD4 naïve cells Th0 cells in T helper type 17 Th17 cells 9 which are considered pivotal players in autoimmunity 10 The IL-23 receptor IL-23R is a heterodimeric receptor composed of 2 subunits IL-12Rβ1 in common with the IL-12 receptor IL-12R and IL-23Rα specific to IL-23 signaling 11 The Th17 subset of T-helper cells is pro-inflammatory plays vital roles in host defense and is involved in the pathogenesis of RA primarily by secreting IL-17 12

SNP is a single base pair mutation at a specific locus usually consisting of two alleles where the rare allele frequency is 1 The genetic factors account for 50-60 of all RA cases 13 Some researchers have reported the relationship between IL-23R gene polymorphisms and RA risk but got no consistent results Therefore this study will search the role of IL-23R gene rs11209026 polymorphisms in individual susceptibility to RA Many different genetic variants with functional gene polymorphisms may play a culprit role in the underlying pathogenetic mechanisms 14

IL-23R gene variants increase susceptibilities to autoimmune disease in patients with psoriasis inflammatory bowel disease and multiple sclerosis 15 IL-17A is a promising target for anti-cytokine therapy in autoimmune arthritis 16

In recent years the associations between IL-17A polymorphisms and RA risk have been studied in various populations by many researchers 17 with the most frequent variant being IL-17A rs2275913

The IL-17A rs2275913 polymorphism is located in the promoter region of the IL-17A gene and cells with the 197A positive allele genotypes GAAA secreted more IL-17A than cells with the 197A negative allele 18

Hence the IL-17A rs2275913 polymorphism results in more efficient secretion of IL-17A which may be a potential mechanism by which this polymorphism can increase the risk of developing RA Many studies hypothesized that rs2201841 and rs2275913 SNP of IL-23R and IL-17A genes respectively have good prediction role for RA susceptibility and severity Genetic and experimental data support the concept that the activation of IL-23IL-17 axis contributes to the development of a series of inflammatory rheumatic diseases including rheumatoid arthritis RA It rapidly became a critical target of research to determine predictors of severity to guide therapeutic intervention

Study Oversight

Has Oversight DMC: None
Is a FDA Regulated Drug?: False
Is a FDA Regulated Device?: False
Is an Unapproved Device?: None
Is a PPSD?: None
Is a US Export?: None
Is an FDA AA801 Violation?: None