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
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
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