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      Difference of IFI44L methylation and serum IFN-a1 level among patients with discoid and systemic lupus erythematosus and healthy individuals

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          Abstract

          Lupus erythematosus (LE) is an autoimmune disease that can be divided into two types. The cutaneous lupus erythematosus (CLE), such as discoid LE (DLE), affects only the skin. While the systemic lupus erythematosus (SLE) affects the hematopoietic, renal, and other systems. We previously found that IFI44L methylation could be a biomarker for SLE. Here, we detect the IFI44L methylation by high-resolution melting-quantitative polymerase chain reaction (HRM-qPCR) assay. The positive percentages of SLE, DLE and healthy controls (HC) are 96.00%, 27.45%, 2.00%, if the curve of 25% methylation was used as the threshold of SLE. And we determined the serum IFN-a1 level by enzyme-linked immunosorbent assay (ELISA) in SLE, DLE and HC. The serum concentration of IFN-a1 in patients with SLE was significantly higher than in the DLE (12.63 ​± ​6.38 ​pg/mL vs 7.99 ​± ​2.28 ​pg/mL, P ​< ​0.05) and HC (12.63 ​± ​6.38 ​pg/mL vs 7.17 ​± ​1.86 ​pg/mL, P ​< ​0.05). But the expression level of IFN-a1 in serum was not significantly different between DLE and HC (7.99 ​± ​2.28 ​pg/mL vs 7.17 ​± ​1.86 ​pg/mL, P ​= ​0.5365). This suggests that methylation of IFI44L and serum concentration of IFN-a1 may be used as biomarkers to distinguish DLE from SLE.

          Highlights

          • DNA methylation of the IFI44L promoter region in SLE patients was significantly decreased compared with DLE patients and HC.

          • The serum concentration of IFN-a1 in SLE patients was significantly higher than in the DLE patients and HC.

          • DNA methylation of IFI44L and serum concentration of IFN-a1 may be used as biomarkers to distinguish DLE from SLE.

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          Most cited references21

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          IFI44L promoter methylation as a blood biomarker for systemic lupus erythematosus.

          Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease with limited reliable diagnostic biomarkers. We investigated whether gene methylation could meet sensitivity and specificity criteria for a robust biomarker.
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            Interferon alpha as a primary pathogenic factor in human lupus.

            Interferon alpha (IFN-α) is a critical mediator of human systemic lupus erythematosus (SLE). This review will summarize evidence supporting the role for IFN-α in the initiation of human SLE. IFN-α functions in viral immunity at the interface of innate and adaptive immunity, a position well suited to setting thresholds for autoimmunity. Some individuals treated with IFN-α for chronic viral infections develop de novo SLE, which frequently resolves when IFN-α is withdrawn, supporting the idea that IFN-α was causal. Abnormally high IFN-α levels are clustered within SLE families, suggesting that high serum IFN-α is a heritable risk factor for SLE. Additionally, SLE-risk genetic variants in the IFN-α pathway are gain of function in nature, resulting in either higher circulating IFN-α levels or greater sensitivity to IFN-α signaling in SLE patients. A recent genome-wide association study has identified additional novel genetic loci associated with high serum IFN-α in SLE patients. These data support the idea that genetically determined endogenous elevations in IFN-α predispose to human SLE. It is possible that some of these gain-of-function polymorphisms in the IFN-α pathway are useful in viral defense, and that risk of SLE is a burden we have taken on in the fight to defend ourselves against viral infection.
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              The interferon-regulated gene signature is elevated in subacute cutaneous lupus erythematosus and discoid lupus erythematosus and correlates with the cutaneous lupus area and severity index score.

              There is increased expression of type I interferon (IFN)-regulated proteins in the blood and target tissues of patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). Patients with SLE have increased IFN-regulated gene expression pointing towards a possible underlying genetic defect.
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                Author and article information

                Contributors
                Journal
                J Transl Autoimmun
                J Transl Autoimmun
                Journal of Translational Autoimmunity
                Elsevier
                2589-9090
                01 March 2021
                2021
                01 March 2021
                : 4
                : 100092
                Affiliations
                [a ]Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
                [b ]Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China
                [c ]Research Unit of Key Technologies of Diagnosis and Treatment for Immune-related Skin Diseases, Chinese Academy of Medical Sciences (2019RU027), Changsha, Hunan, China
                Author notes
                []Corresponding author. Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China #12 Jiang Wangmiao Street, 210000, China. qianlu5860@ 123456pumcderm.cams.cn
                [∗∗ ]Corresponding author. Department of Dermatology, Second Xiangya Hospital, Central South University, #139 Renmin Middle Road, Changsha, Hunan, 410011, China. zhaoming307@ 123456csu.edu.cn
                Article
                S2589-9090(21)00012-5 100092
                10.1016/j.jtauto.2021.100092
                7972957
                fdfe1f57-2c05-4e03-bfff-930f6fc6c9db
                © 2021 The Authors. Published by Elsevier B.V.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 19 January 2021
                : 20 February 2021
                : 21 February 2021
                Categories
                Research paper

                discoid lupus erythematosus,systemic lupus erythematosus,ifi44l,dna methylation,hrm-qpcr,ifn-a1

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