Association of interleukin-17A gene polymorphisms and susceptibility to systemic lupus erythematosus in Egyptian children and adolescents: a multi-centre study

Elkoumi, Mohamed A.; Allah, Mayy A.N.; Mohamed, Faisal Y; Boraey, Naglaa F; Abdellatif, Sawsan H.; Shehab, Mona; Sherif, Ahmed H.; Akeel, Nagwa E.; Saleh, Rabab; Elshreif, Anas M.; Abdelrahman, Hind M.; Soliman, Attia A.; Emam, Ahmed A.; Youssef, Manal A.; Fahmy, Dalia S.; Sallam, Mohammad M.; Nawara, Abdallah; Elgohary, Elsayed A.; Ismael, Ali; El-Kaffas, Sameh MH; Sobeih, Alaa A.; Ibrahim, Lamya; Ibrahim, Mohamed; Abdou, Adel M.; Yousry, Sherif M.; Osman, Sherif; Eldeeb, Fatma; Elhewala, Ahmed; Hafez, Sahbaa F. M.; Waked, Nevin M; Elbasyouni, H A A; Fouad, Rania A; Zeid, Ahmed; Nashat, Mohamed; Farghaly, Mohsen A.A.

doi:10.1177/0961203320922305

Cited by 3 publications

(3 citation statements)

References 40 publications

(54 reference statements)

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“…Other studies were performed on Egyptian population regarding A allele frequency of IL-17A rs2275913 polymorphism in Egyptian population. The targeted patients in these studies were those with systemic lupus erythematosus [ 41 ], acute myeloid leukemia [ 42 ] and vitiligo [ 43 ]. Similar to our study and Aziz et al, 2018 study [ 27 ], their reported frequencies were 65% within healthy control group in the study concerned about acute myeloid leukemia patients and 53.8% within healthy control group in vitiligo concerned one.…”

Section: Discussionmentioning

confidence: 99%

IL-23/Th17 pathway and IL-17A gene polymorphism in Egyptian children with immune thrombocytopenic purpura

et al. 2021

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Background Immune thrombocytopenic purpura (ITP) is an acquired complex autoimmune thrombocytopenia. Uncontrolled cellular immune response is one of the key triggers for the loss of immune tolerance in ITP patients. The purpose of this study was to investigate the association of IL-23/Th17, IL-17A and IL-17A rs2275913 gene polymorphism with ITP in Egyptian children. Methods 60 patients with ITP and 50 healthy control children from Minia city- Egypt were involved. Serum levels of IL-23 and IL-17A were determined by enzyme-linked immunosorbent assay. The frequency of Th17 cells was measured using flow cytometer. Genotyping for IL-17A was performed via polymerase chain reaction-restriction fragment length polymorphism. Results Comparing children with ITP to controls, serum levels of IL-23 and IL-17A as well as Th17 cells percentage were significantly increased (p < 0.001). Also, higher levels of these ILs and Th17 cells percentage were associated with decreased platelet count within ITP patients (p < 0.001). Analysis of genotype frequencies for IL-17A rs2275913 polymorphism and its alleles (A, G) showed no significant difference between cases and controls. Likewise, no significant differences were demonstrated between acute and chronic ITP regarding both IL-17A rs2275913 polymorphism prevalence and levels of IL-23, IL-17A plus Th17 cells percentage. The frequency of A alleles was 85 and 86% within patients and controls, respectively. Conclusions Elevated levels of IL-23, IL-17A and Th17 cells may be involved in ITP pathogenesis while IL-17A polymorphism rs2275913 is not prevalent in Egyptian children with ITP.

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Section: Discussionmentioning

confidence: 99%

IL-23/Th17 pathway and IL-17A gene polymorphism in Egyptian children with immune thrombocytopenic purpura

et al. 2021

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“…Based on the inclusion and exclusion criteria, six studies were found suitable for the present analysis. However, one of the studies 25 had included juvenile onset systemic lupus erythematosus patients, thus not included in the meta-analysis. In addition, another independent study in the Indonesian population 37 was excluded from the statistical analysis as the IL-17A rs2275913 genotypes distribution deviated from the HWE (χ 2 =6.80, p = 0.009).…”

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confidence: 99%

“…The rs2275913 polymorphism (G>A) is situated in the IL-17A promoter region (À197) and linked with plasma IL-17A levels. [23][24][25][26] Since the promoter polymorphism in the IL-17A gene (rs2275913) affects the levels of IL-17A and pro-inflammatory cytokines, IL-17A is believed to play a critical role in the pathogenesis of SLE; various population-based genetic association studies have been conducted in various cohorts to decipher the association of IL-17A rs2275913 with susceptibility to develop SLE. The findings of the case-control studies, on the other hand, remained equivocal.…”

Section: Introductionmentioning

confidence: 99%

Interleukin 17A rs2275913 polymorphism is associated with susceptibility to systemic lupus erythematosus: A meta and trial sequential analysis

Padhi

Sarangi

Nayak

et al. 2022

Lupus

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Background The role of cytokines in the development of systemic lupus erythematosus (SLE) has received much attention. Interleukin-17 A upregulates several inflammation-related genes and is thought to have a crucial role in SLE development. The susceptibility to SLE development has been linked to functional genetic variations of the IL-17A gene; nevertheless, the findings have been conflicting. We conducted a meta-analysis that included previously published reports to establish a definitive conclusion on the role of the IL-17A rs2275913 polymorphism in SLE propensity. Materials and Methods The PubMed, Google Scholar, and Scopus databases were used to find eligible published articles. All analyses were conducted using Comprehensive Meta-analysis V3.1. Funnel plots and Egger’s regression analysis were used to assess publication bias. Q statistics and I2 test explored the heterogeneity among the included studies. Combined odds ratio, 95% confidence interval were calculated for each comparison model. Results Based on the inclusion and exclusion criteria, a total of four reports, comprising of 608 SLE patients and 815 healthy controls, were considered for the present meta-analysis. The homozygous comparison (AA vs. GG: combined odds ratio= 2.046, p = 0.005) and recessive genetic model (AA vs. GG+GA: combined odds ratio=1.901, p = 0.010) analysis revealed a significant association of rs2275913 with susceptibility to the development of SLE. However, other genetic comparisons (A vs. G, GA vs. GG, AA+GA vs. GG) failed to demonstrate such association. Furthermore, trial sequential analysis revealed a sufficient number of studies, including enough cases and controls that have already been considered to conclude the role of IL17-A rs2275913 polymorphism in SLE. Conclusions IL-17A rs2275913 polymorphism is associated with susceptibility to SLE development.

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The Th17/IL-17 Axis and Kidney Diseases, With Focus on Lupus Nephritis

Paquissi

Abensur

2021

Front. Med.

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Systemic lupus erythematosus (SLE) is a disease characterized by dysregulation and hyperreactivity of the immune response at various levels, including hyperactivation of effector cell subtypes, autoantibodies production, immune complex formation, and deposition in tissues. The consequences of hyperreactivity to the self are systemic and local inflammation and tissue damage in multiple organs. Lupus nephritis (LN) is one of the most worrying manifestations of SLE, and most patients have this involvement at some point in the course of the disease. Among the effector cells involved, the Th17, a subtype of T helper cells (CD4+), has shown significant hyperactivation and participates in kidney damage and many other organs. Th17 cells have IL-17A and IL-17F as main cytokines with receptors expressed in most renal cells, being involved in the activation of many proinflammatory and profibrotic pathways. The Th17/IL-17 axis promotes and maintains repetitive tissue damage and maladaptive repair; leading to fibrosis, loss of organ architecture and function. In the podocytes, the Th17/IL-17 axis effects include changes of the cytoskeleton with increased motility, decreased expression of health proteins, increased oxidative stress, and activation of the inflammasome and caspases resulting in podocytes apoptosis. In renal tubular epithelial cells, the Th17/IL-17 axis promotes the activation of profibrotic pathways such as increased TGF-β expression and epithelial-mesenchymal transition (EMT) with consequent increase of extracellular matrix proteins. In addition, the IL-17 promotes a proinflammatory environment by stimulating the synthesis of inflammatory cytokines by intrinsic renal cells and immune cells, and the synthesis of growth factors and chemokines, which together result in granulopoiesis/myelopoiesis, and further recruitment of immune cells to the kidney. The purpose of this work is to present the prognostic and immunopathologic role of the Th17/IL-17 axis in Kidney diseases, with a special focus on LN, including its exploration as a potential immunotherapeutic target in this complication.

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Association of interleukin-17A gene polymorphisms and susceptibility to systemic lupus erythematosus in Egyptian children and adolescents: a multi-centre study

Cited by 3 publications

References 40 publications

IL-23/Th17 pathway and IL-17A gene polymorphism in Egyptian children with immune thrombocytopenic purpura

IL-23/Th17 pathway and IL-17A gene polymorphism in Egyptian children with immune thrombocytopenic purpura

Interleukin 17A rs2275913 polymorphism is associated with susceptibility to systemic lupus erythematosus: A meta and trial sequential analysis

The Th17/IL-17 Axis and Kidney Diseases, With Focus on Lupus Nephritis

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