Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05570513 |
| Other study ID # |
IL23 and IL17A in RA |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
August 4, 2023 |
| Est. completion date |
August 4, 2026 |
Study information
| Verified date |
September 2022 |
| Source |
Assiut University |
| Contact |
Asmaa Salah |
| Phone |
01032130812 |
| Email |
asmaa.elprins[@]gmail.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial 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 .
Description:
Rheumatoid arthritis an autoimmune disease that is associated with progressive disability,
systemic complications and socioeconomic costs. RA affects 0.5-1% 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 3:1 (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 gamma/delta 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 GA/AA) 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-23/IL-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 .
