The roles of ERAP1 and ERAP2 in autoimmunity and cancer immunity: New insights and perspective

Babaie, Farhad; Hosseinzadeh, Reza; Ebrazeh, Mehrdad; Seyfizadeh, Nayer; Aslani, Saeed; Salimi, Soraya; Hemmatzadeh, Maryam; Azizi, Gholamreza; Jadidi‐Niaragh, Farhad; Mohammadi, Hamed

doi:10.1016/j.molimm.2020.02.020

Cited by 42 publications

(34 citation statements)

References 174 publications

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“…To date, large‐scale analyses have found over 60 genetic loci for AS risk, even though most investigations have assigned a large proportion of genetic‐related risk of AS to the HLA‑B27 gene 3,27 . Investigations on the SNPs of the ERAP2 gene in the context of AS risk are scarce.…”

Section: Discussionmentioning

confidence: 99%

Association of the genetic variants in the endoplasmic reticulum aminopeptidase 2 gene with ankylosing spondylitis susceptibility

et al. 2021

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Background Genetic polymorphisms in the endoplasmic reticulum aminopeptidase gene ERAP2 has been attributed with the etiopathogenesis of ankylosing spondylitis (AS). Here we assessed the association of ERAP2 gene single nucleotide polymorphisms (SNPs) with AS predisposition in Iranian patients and determined their effect on the inflammatory state of the patients. Methods For genotyping of rs2548538, rs2287988, and rs17408150 SNPs using a real‐time allelic discrimination approach, DNA was extracted from the whole blood of 250 AS patients and 250 healthy individuals. RNA of the peripheral blood mononuclear cells was separated, cDNA was synthesized, and transcriptional levels of cytokines, including interleukin (IL)‐17A, IL‐23, IL‐10, and transforming growth factor‐β, were measured. Enzyme‐linked immunosorbent assay was used to measure the serum concentration on the cytokines. Results Three ERAP2 gene SNPs were not associated significantly with AS risk. Nonetheless, rs2287988 and rs17408150 SNPs showed statistically significant association with susceptibility to the disease in those AS patients who were positive for human leukocyte antigen (HLA)‐B27. Transcriptional level and serum concentration of IL‐17A and IL‐23 were higher, but those of IL‐10 were lower in both AS patients and the HLA‐B27‐positive patient group relative to the control group. Nevertheless, ERAP2 gene SNPs in the HLA‐B27‐positive AS patients did not affect the transcription level and serum concentration of cytokines. Conclusions ERAP2 gene rs2287988 and rs17408150 SNPs are associated with susceptibility to AS, but they are probably not determining the levels of IL‐17A, IL‐23, and IL‐10 in this disease.

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Section: Discussionmentioning

confidence: 99%

Association of the genetic variants in the endoplasmic reticulum aminopeptidase 2 gene with ankylosing spondylitis susceptibility

et al. 2021

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“…To date, large scale analyses have found over 60 genetic loci for AS risk, even though a bulk of investigations have assigned a large proportion of genetic-related risk of AS to the HLA-B27 gene (3,26). There is paucity of investigations on the SNPs of the ERAP2 gene in the context of AS risk.…”

Section: Discussionmentioning

confidence: 99%

Association of the genetic variants in the Endoplasmic reticulum aminopeptidase 2 gene with ankylosing spondylitis susceptibility

Ebrazeh

Ezzatifar

Torkamandi

et al. 2020

Preprint

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Background: Genetic polymorphisms in the Endoplasmic reticulum aminopeptidase (ERAP) 2 gene has been attributed with the Ankylosing spondylitis (AS) etiopathogenesis. Here we assessed the association of ERAP2 gene single nucleotide polymorphisms (SNPs) with AS predisposition in Iranian patients and determined their effect on the inflammatory state of the patients.Methods: For genotyping of rs2548538, rs2287988, and rs17408150 SNPs using Real-time allelic discrimination approach, DNA was extracted from the whole blood of 250 AS patients and 250 healthy subjects. RNA of the peripheral blood mononuclear cells (PBMCs) was separated, cDNA was synthesized, and transcriptional levels of cytokines, including interleukin (IL)-17A, IL-23, IL-10, and transforming growth factor (TGF)-β were measured. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum concentration on the cytokines.Results: Three ERAP2 gene SNPs were not associated significantly with AS risk. Nonetheless, rs2287988 and rs17408150 SNPs showed statistically significant association with susceptibility to the disease in those AS subjects who were positive to Human leukocyte antigen (HLA)-B27. Transcriptional level and serum concentration of IL-17A and IL-23 were higher, while those of IL-10 were lower in both AS patients and HLA-B27 positive patient group relative to control group. Nevertheless, ERAP2 gene SNPs in the HLA-B27 positive AS patients did not affect the transcriptional level and serum concentration of cytokines.Conclusions: ERAP2 gene rs2287988 and rs17408150 SNP are associated with susceptibility to AS, but they probably are not determining the levels of IL-17A, IL-23, and IL-10 in this disease.

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“…ERAP1 is highly polymorphic, with variants that alter the peptide trimming activity, specificity, and expression, even if they reside far from the active site region. Several ERAP1 genetic variants have been associated with multiple human leukocyte antigen (HLA) class I autoinflammatory disorders, including ankylosing spondylitis (AS), BD, psoriasis, multiple sclerosis (MS), and type I diabetes, as well as essential hypertension and susceptibility to infectious disease, such as human papilloma virus (HPV)-induced cancer, HIV, hepatitis C virus (HCV), and HCMV infection [55][56][57]. In the context of autoimmune diseases, these genetic changes contribute to immune dysregulation in individuals with a specific HLA class I background [57].…”

Section: Functional Consequences Of Erap1 Polymorphisms In Human Disementioning

confidence: 99%

“…The intronic variants rs149481, rs27042, rs149173, and rs17481856 have been associated with susceptibility to Toxoplasma gondii infection, Kawasaki disease, chronic hepatitis C, and HIV [59,60]. Interestingly, most of these SNPs have also been associated with essential hypertension and autoimmune diseases, including AS, MS, psoriasis, and BD [56,59,60].…”

Section: Functional Consequences Of Erap1 Polymorphisms In Human Disementioning

confidence: 99%

Impact of Natural Occurring ERAP1 Single Nucleotide Polymorphisms within miRNA-Binding Sites on HCMV Infection

D’Amico

Tempora

Lucarini

et al. 2020

IJMS

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Human cytomegalovirus (HCMV) is a β-herpesvirus that causes serious problems in people with a compromised immune system, whereas it coexists asymptomatically within the host with a healthy immune system. Like other viruses, HCMV has adopted multiples strategies to manipulate the host’s immune responses. Among them, expression of viral microRNAs (miRNAs) is one of the most intriguing. HCMV miR-UL112-5p and miR-US4-1 have been found to contribute to immune evasion by targeting the endoplasmic reticulum aminopeptidase 1 (ERAP1), a highly polymorphic key component of antigen processing. The current incomplete picture on the interplay between viral miRNAs and host immunity implies the need to better characterize the host genetic determinants. Naturally occurring single nucleotide polymorphisms (SNPs) within the miRNA binding sites of target genes may affect miRNA–target interactions. In this review, we focus on the relevance of 3′ untranslated region (3′UTR) ERAP1 SNPs within miRNA binding sites in modulating miRNA–mRNA interactions and the possible consequent individual susceptibility to HCMV infection. Moreover, we performed an in silico analysis using different bioinformatic algorithms to predict ERAP1 variants with a putative powerful biological function. This evidence provides a basis to deepen the knowledge on how 3′UTR ERAP1 variants may alter the mechanism of action of HCMV miRNAs, in order to develop targeted antiviral therapies.

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The roles of ERAP1 and ERAP2 in autoimmunity and cancer immunity: New insights and perspective

Cited by 42 publications

References 174 publications

Association of the genetic variants in the endoplasmic reticulum aminopeptidase 2 gene with ankylosing spondylitis susceptibility

Association of the genetic variants in the endoplasmic reticulum aminopeptidase 2 gene with ankylosing spondylitis susceptibility

Association of the genetic variants in the Endoplasmic reticulum aminopeptidase 2 gene with ankylosing spondylitis susceptibility

Impact of Natural Occurring ERAP1 Single Nucleotide Polymorphisms within miRNA-Binding Sites on HCMV Infection

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