Interleukin 7 receptor T244I polymorphism and the multiple sclerosis susceptibility: a meta-analysis

Sahami-Fard, Mohammad Hossein; Mozhdeh, Mahya; Izadpanah, Fatemeh; Kashani, Hamed Haddad; Nezhadi, Akram

doi:10.1016/j.jneuroim.2020.577166

Cited by 9 publications

(6 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, they concluded that the rs6897932 SNP might be a risk factor for MS in Europe but not in the Middle East. 101 A growing body of evidence indicates that ethnicity might impact clinical manifestations of MS, possibly leading to different phenotypes of the disease. 102,103 Interestingly, despite not demonstrating an association with susceptibility to develop MS, some groups have observed that rs6897932 SNP is associated with greater disease severity.…”

Section: Multiple Sclerosis (Ms) and Other Demyelinating Autoimmune Dmentioning

confidence: 99%

Soluble IL-7Rα/sCD127 in Health, Disease, and Its Potential Role as a Therapeutic Agent

Barros¹,

Berthoud²,

Aloufi³

et al. 2021

ITT

View full text Add to dashboard Cite

Soluble cytokine receptors can influence immune responses by modulating the biological functions of their respective ligands. These effects can be either agonistic or antagonistic and a number of soluble cytokine receptors have been shown to play critical roles in both maintenance of health and disease pathogenesis. Soluble IL-7Ra (sCD127) is one such example. With its impact on the IL-7/CD127 pathway, which is fundamental for the development and homeostasis of T cells, the role of sCD127 in health and disease has been extensively studied in recent years. Within this review, the role of sCD127 in maintaining host immune function is presented. Next, by addressing genetic factors affecting sCD127 expression and the associated levels of sCD127 production, the roles of sCD127 in autoimmune disease, infections and cancer are described. Finally, advances in the field of soluble cytokine therapy and the potential for sCD127 as a biomarker and therapeutic agent are discussed.

show abstract

Section: Multiple Sclerosis (Ms) and Other Demyelinating Autoimmune Dmentioning

confidence: 99%

Soluble IL-7Rα/sCD127 in Health, Disease, and Its Potential Role as a Therapeutic Agent

Barros¹,

Berthoud²,

Aloufi³

et al. 2021

ITT

View full text Add to dashboard Cite

show abstract

“…Interestingly, we did not observe an increase in soluble IL-7Rα isoform abundance in the healthy donors homozygous for the C allele versus those carrying the c.731C > T SNP. Studies investigating the rs6897932 SNP have shown that this risk allele appears to be associated with MS only in the European population, but not in Turkish nor Middle Eastern populations [ 31 , 32 ]. It is plausible that another factor, e.g.…”

Section: Discussionmentioning

confidence: 99%

Novel Synonymous Variant in IL7R Causes Preferential Expression of the Soluble Isoform

Mackeh,

El Bsat,

Elmi

et al. 2024

J Clin Immunol

View full text Add to dashboard Cite

Purpose The interleukin-7 receptor (IL-7R) is primarily expressed on lymphoid cells and plays a crucial role in the development, proliferation, and survival of T cells. Autosomal recessive mutations that disrupt IL-7Rα chain expression give rise to a severe combined immunodeficiency (SCID), which is characterized by lymphopenia and a T−B+NK+ phenotype. The objective here was to diagnose two siblings displaying the T−B+NK+ SCID phenotype as initial clinical genetic testing did not detect any variants in known SCID genes. Methods Whole genome sequencing (WGS) was utilized to identify potential variants causing the SCID phenotype. Splicing prediction tools were employed to assess the deleterious impact of the mutation. Polymerase Chain Reaction (PCR), Sanger sequencing, flow cytometry, and ELISA were then used to validate the pathogenicity of the detected mutation. Results We discovered a novel homozygous synonymous mutation in the IL7R gene. Our functional studies indicate that this variant is pathogenic, causing exon 6, which encodes the transmembrane domain, to be preferentially spliced out. Conclusion In this study, we identified a novel rare synonymous mutation causing a loss of IL-7Rα expression at the cellular membrane. This case demonstrates the value of reanalyzing genetic data based on the clinical phenotype and highlights the significance of functional studies in determining the pathogenicity of genetic variants.

show abstract

“…IL7 has a range of biological activities and is essential for the survival, proliferation, and homeostasis of T-cells. It is also a factor in bone marrow culture that can induce the proliferation of B progenitor cells 13 . IL7R may also have a primary signaling function through the autoimmunity cascade.…”

Section: Introductionmentioning

confidence: 99%

Expression and clinical significance of IL7R, NFATc2, and RNF213 in familial and sporadic multiple sclerosis

Imani

Hojati

Khalilian

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a chronic inflammatory and autoimmune disorder of the central nervous system characterized by myelin loss and axonal dysfunction. Increased production of inflammatory factors such as cytokines has been implicated in axon destruction. In the present study, we compared the expression level of IL7R, NFATc2, and RNF213 genes in the peripheral blood of 72 MS patients (37 familial MS, 35 sporadic MS) and 74 healthy controls (34 individuals with a family history of the disease, 40 healthy controls without a family history) via Real-time PCR. Our results showed that the expression level of IL7R was decreased in the sporadic patients in comparison with other groups. Additionally, there was an increased NFATc2 expression level in MS patients versus healthy controls. Increased expression of NFATc2 in sporadic and familial groups compared to the controls, and familial group versus FDR was also seen. Our results also represented an increased expression level of RNF213 in familial patients as compared to the control group. The similar RNF213 expression between sporadic and control group, as well as FDR and familial group was also seen. Diagnostic evaluation was performed by receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) calculation. The correlation of clinical parameters including onset age and Expanded Disability Status Scale (EDSS) with our gene expression levels were also assessed. Overall, decreased expression level of IL7R in the sporadic cases and increased expression level of NFATc2 may be associated with the pathogenesis of MS disease. Confirmation of the effects of differential expression of RNF213 gene requires further studies in the wider statistical populations.

show abstract

Interleukin 7 receptor T244I polymorphism and the multiple sclerosis susceptibility: a meta-analysis

Cited by 9 publications

References 41 publications

Soluble IL-7Rα/sCD127 in Health, Disease, and Its Potential Role as a Therapeutic Agent

Soluble IL-7Rα/sCD127 in Health, Disease, and Its Potential Role as a Therapeutic Agent

Novel Synonymous Variant in IL7R Causes Preferential Expression of the Soluble Isoform

Expression and clinical significance of IL7R, NFATc2, and RNF213 in familial and sporadic multiple sclerosis

Contact Info

Product

Resources

About