Genetic Polymorphisms in Genes Involved in the Type I Interferon System (IFIH1/MDA-5, TNFAIP3/A20, and STAT4): Association with SLE Risk in Egyptian Children and Adolescents

Zedan, Mohamed M; Attia, Zeinab R.; Azeem, Rania A. Abd El; Mutawi, Thuraya M; Shehawy, Amora S El; Bakr, Ashraf M.

doi:10.2147/jir.s309008

Cited by 7 publications

(3 citation statements)

References 38 publications

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“…Although IFIH1, RSAD2, and PARP9 were found to be associated with a variety of autoimmune or inflammatory disease development, such as SLE, RA, Sjögren’s syndrome (SS), type 1 diabetes (T1D), and AITD ( Frommer and Kahaly, 2021 ; Zedan et al, 2021 ), we did not find that these genes were differentially expressed between the recurrent GD group and the normal group. Ubiquitin-specific peptidase 18 (USP18) plays a crucial role in the development of Th17 cells and can regulate the differentiation and function of Treg cells ( Yang et al, 2021 ).…”

Section: Discussioncontrasting

confidence: 68%

Identification of lncRNA and mRNA Expression Profile in Relapsed Graves’ Disease

Yao

Song

Wang

et al. 2021

Front. Cell Dev. Biol.

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Background: Graves’ disease (GD) is a common autoimmune disease, and its pathogenesis is unclear. Studies have found that the occurrence of GD is related to the immune disorder caused by the interaction of genetic susceptibility and environmental factors. The CD4+ T cell subset is closely related to the immune disorder of GD. LncRNAs are RNA molecules with a length of more than 200 nt and are involved in a variety of autoimmune diseases. However, the roles of lncRNAs in recurrent GD are still elusive. The purpose of this study is to identify lncRNA and mRNA expression profile in relapsed Graves’ disease.Method: CD4+ T cells from 12 recurrent GD and 8 healthy controls were collected for high-throughput sequencing. The gene-weighted co-expression network analysis (WGCNA) was used to construct the co-expression module relevant to recurrent GD, and the key genes in the module were verified by RT-PCR.Results: There are 602 upregulated lncRNAs and 734 downregulated lncRNAs in CD4+ T cells in recurrent GD patients compared with the healthy controls. The module most relevant to GD recurrence was constructed using WGCNA, and the key genes in the module were verified by RT-PCR. We found that the expression of RPL8, OAS2, NFAT5, DROSHA, NONHSAT093153.2, NONHSAT118924.2, and NONHSAT209004.1 was significantly decreased in GD group (p < 0.001, p < 0.001, p < 0.01, p < 0.05, p < 0.001, p < 0.05, and p < 0.01, respectively).Conclusion: LncRNAs are closely related to the recurrence of GD. For the first time, we constructed the expression profile of lncRNAs and mRNAs in CD4+ T cells in recurrent GD patients.

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Section: Discussioncontrasting

confidence: 68%

Identification of lncRNA and mRNA Expression Profile in Relapsed Graves’ Disease

Yao

Song

Wang

et al. 2021

Front. Cell Dev. Biol.

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“…Genome wide association studies in SLE patients has demonstrated single nucleotide polymorphisms (SNPs) in loci near IFN related genes, in particular interferon regulatory factor 5 (IRF5), IRF7, IRF8, STAT4 and Tyk2, that are associated with the risk of developing SLE in adults ( Sigurdsson et al, 2005 ; Graham et al, 2007 ). Consistent with these observations, using a candidate gene approach of type I IFN related genes, the T allele of rs3747517 in the IFIH1 gene was associated with a reduced risk of SLE while the T allele of rs7574865 in STAT4 was associated with an increased risk of developing SLE in children and adolescents ( Zedan et al, 2021 ). In conjunction with our understanding of type I IFN in mouse models with SLE and translational studies demonstrating increased expression of type I IFN and related pathways in SLE, these genetic studies strongly support an important role for type I IFN related pathways in SLE pathogenesis and the potential for translation of these findings to the care of patients with SLE.…”

Section: Biology and Function Of Type I Interferonsmentioning

confidence: 62%

Targeting type I interferons in systemic lupus erythematous

et al. 2023

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Systemic lupus erythematosus (SLE) is a complex autoimmune disease with systemic clinical manifestations including, but not limited to, rash, inflammatory arthritis, serositis, glomerulonephritis, and cerebritis. Treatment options for SLE are expanding and the increase in our understanding of the immune pathogenesis is leading to the development of new therapeutics. Autoantibody formation and immune complex formation are important mediators in lupus pathogenesis, but an important role of the type I interferon (IFN) pathway has been identified in SLE patients and mouse models of lupus. These studies have led to the development of therapeutics targeting type I IFN and related pathways for the treatment of certain manifestations of SLE. In the current narrative review, we will discuss the role of type I IFN in SLE pathogenesis and the potential translation of these data into strategies using type I IFN as a biomarker and therapeutic target for patients with SLE.

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“…3 Among Egyptian patients, different genetic polymorphisms have been studied and found to be associated with SLE as polymorphisms in the gene coding for the autoimmune regulator (AIRE), type I interferon (IFN) pathway, interleukin 27, programmed cell death 1 (PD1), tumor necrosis factor (TNF-α) and IFN-γ. [4][5][6][7][8] However, the role of the human leukocyte antigen-G (HLA-G) gene has not been addressed before among Egyptian patients.…”

Section: Introductionmentioning

confidence: 99%

Immunogenetic Relationship of HLA-G 14 bp Insertion/Deletion Polymorphism and Toll-Like Receptor 9 with Systemic Lupus Erythematosus in Egyptian Patients: A Case-Control Study

Mohammed¹,

Kady²,

Boghdadi³

et al. 2022

IJGM

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Introduction The level of expression of the immunoregulatory human leukocyte antigen-G (HLA-G) has been suggested to play a role in the immunopathogenesis of systemic lupus erythematosus (SLE). A 14 bp insertion/deletion (ins/del) polymorphism in the 3ˊuntranslated region of HLA-G gene may influence the level of expression. The role of Toll-like receptor 9 (TLR9) in the pathogenesis of SLE has been highlighted. Data among Egyptian patients are quite limited. Purpose To detect the association of HLA-G 14 bp ins/del gene polymorphism with the susceptibility to SLE and to correlate TLR9 serum level with disease activity among Egyptian patients. Patients and Methods A case-control study that included 102 SLE female patients and 102 healthy matched volunteers as controls was carried out. Disease activity in patients was determined using the modified Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). HLA-G 14 bp ins/del genotype was detected by polymerase chain reaction (PCR). TLR9 serum level was estimated using enzyme-linked immunosorbent assay (ELISA) technique. Results The ins/ins genotype was significantly increased among SLE patients compared to healthy subjects (58.8% vs 9.8%; odds ratio [OR] = 11.79, P < 0.001). The 14 bp ins allele was significantly more frequent in SLE patients than in healthy subjects (65.7% vs 27.9%, respectively) and significantly associated with an increased risk of SLE (OR 4.94, P < 0.001). The mean TLR9 serum level showed a significant increase in SLE patients compared to healthy subjects (397.04±137.86 vs 195.22±45.14 ng/L, p < 0.001) and was significantly associated with disease activity as well as to patients’ HLA-G genotypes (p < 0.001). Conclusion Among Egyptian population, HLA-G 14 bp ins/ins homozygous genotype and ins allele may constitute a potential risk for SLE susceptibility, while TLR9 serum level is significantly associated with disease activity.

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Genetic Polymorphisms in Genes Involved in the Type I Interferon System (IFIH1/MDA-5, TNFAIP3/A20, and STAT4): Association with SLE Risk in Egyptian Children and Adolescents

Cited by 7 publications

References 38 publications

Identification of lncRNA and mRNA Expression Profile in Relapsed Graves’ Disease

Identification of lncRNA and mRNA Expression Profile in Relapsed Graves’ Disease

Targeting type I interferons in systemic lupus erythematous

Immunogenetic Relationship of HLA-G 14 bp Insertion/Deletion Polymorphism and Toll-Like Receptor 9 with Systemic Lupus Erythematosus in Egyptian Patients: A Case-Control Study

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