Epigenetic Mechanisms and Posttranslational Modifications in Systemic Lupus Erythematosus

Quiroz, Elkin Navarro; Chavez-Estrada, Valeria; Macias-Ochoa, Karime; Ayala-Navarro, María Fernanda; Flores-Aguilar, Aniyensy Sarai; Morales-Navarrete, Francisco; Lopez, Fernando de la Cruz; Escorcia, Lorena Gomez; Musso, Carlos Guido; Aroca, Gustavo; Torres, Henry Gonzales; Pérez, Anderson Díaz; Bonfanti, Andrés Cadena; Gutierrez, Joany Sarmiento; Meza, Jainy; Arroyo, Esperanza Diaz; Lemus, Yesit Bello; Ahmad, Mostapha; Quiroz, Roberto Navarro

doi:10.3390/ijms20225679

Cited by 23 publications

(7 citation statements)

References 79 publications

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“…These disorders include rheumatoid arthritis (RA), psoriasis, SLE, Alzheimer’s disease (AD), multiple sclerosis (MS), and cancers [ 68 ]. In SLE, the mechanisms responsible for the loss of immune tolerance have yet to be fully elucidated [ 70 ]; however, epigenetic factors and PTMs are becoming increasingly recognised in the pathogenesis of the disease [ 71 ]. In the context of SLE, the PTM of histone proteins, the loss of tolerance and the initiation of an autoimmune response are consistent features of the disease [ 72 , 73 ].…”

Section: Discussionmentioning

confidence: 99%

Classification of Systemic Lupus Erythematosus Using Raman Spectroscopy of Blood and Automated Computational Detection Methods: A Novel Tool for Future Diagnostic Testing

et al. 2022

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The aim of this study was to explore the proof of concept for using Raman spectroscopy as a diagnostic platform in the setting of systemic lupus erythematosus (SLE). We sought to identify unique Raman signatures in serum blood samples to successfully segregate SLE patients from healthy controls (HC). In addition, a retrospective audit was undertaken to assess the clinical utility of current testing platforms used to detect anti-double stranded DNA (dsDNA) antibodies (n = 600). We examined 234 Raman spectra to investigate key variances between SLE patients (n = 8) and HC (n = 4). Multi-variant analysis and classification model construction was achieved using principal component analysis (PCA), PCA-linear discriminant analysis and partial least squares-discriminant analysis (PLS-DA). We achieved the successful segregation of Raman spectra from SLE patients and healthy controls (p-value < 0.0001). Classification models built using PLS-DA demonstrated outstanding performance characteristics with 99% accuracy, 100% sensitivity and 99% specificity. Twelve statistically significant (p-value < 0.001) wavenumbers were identified as potential diagnostic spectral markers. Molecular assignments related to proteins and DNA demonstrated significant Raman intensity changes between SLE and HC groups. These wavenumbers may serve as future biomarkers and offer further insight into the pathogenesis of SLE. Our audit confirmed previously reported inconsistencies between two key methodologies used to detect anti-dsDNA, highlighting the need for improved laboratory testing for SLE. Raman spectroscopy has demonstrated powerful performance characteristics in this proof-of-concept study, setting the foundations for future translation into the clinical setting.

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Section: Discussionmentioning

confidence: 99%

Classification of Systemic Lupus Erythematosus Using Raman Spectroscopy of Blood and Automated Computational Detection Methods: A Novel Tool for Future Diagnostic Testing

et al. 2022

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“…Ubiquitination, as an important form of the PTM of proteins, regulates protein abundance, activity, subcellular localization, and their interactions, as well as a variety of signaling pathways. Ubiquitination plays a pivotal role in the pathogenesis of SLE (132,133). A phase I clinical trial showed that the expression of Aiolos and Ikaros was significantly higher in patients with SLE than in healthy volunteers.…”

Section: Systemic Lupus Erythematosusmentioning

confidence: 99%

Advances in the potential roles of Cullin-RING ligases in regulating autoimmune diseases

et al. 2023

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Cullin-RING ligases (CRLs) are the largest class of E3 ubiquitin ligases regulating the stability and subsequent activity of a large number of important proteins responsible for the development and progression of various diseases, including autoimmune diseases (AIDs). However, the detailed mechanisms of the pathogenesis of AIDs are complicated and involve multiple signaling pathways. An in-depth understanding of the underlying regulatory mechanisms of the initiation and progression of AIDs will aid in the development of effective therapeutic strategies. CRLs play critical roles in regulating AIDs, partially by affecting the key inflammation-associated pathways such as NF-κB, JAK/STAT, and TGF-β. In this review, we summarize and discuss the potential roles of CRLs in the inflammatory signaling pathways and pathogenesis of AIDs. Furthermore, advances in the development of novel therapeutic strategies for AIDs through targeting CRLs are also highlighted.

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“…The PTMs found in patients with SLE include phosphorylation, methylation, acetylation, isoaspartylation, etc. The proteins susceptible to phosphorylation in SLE are U1 small nuclear ribonucleoprotein (snRNP) 68K [83], SSA/Ro and SSB/La [84,85], spliceosomal Sm protein that is vulnerable to methylation in D1 and D3 subunits [86,87], the frequently ubiquitinated proteinase serine/arginine-rich splicing factor 1 (SKSF1) [88] and myeloperoxidase (MPO) [89,90]. Table 4 lists the histone and non-histone protein modifications in immune-related cells and post-translational molecules in SLE patients.…”

Section: Post-translational Non-histone Protein Modifications In Slementioning

confidence: 99%

Aberrant Non-Coding RNA Expression in Patients with Systemic Lupus Erythematosus: Consequences for Immune Dysfunctions and Tissue Damage

Tsai

Shen

et al. 2020

Biomolecules

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Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease with heterogeneous clinical manifestations. A diverse innate and adaptive immune dysregulation is involved in the immunopathogenesis of SLE. The dysregulation of immune-related cells may derive from the intricate interactions among genetic, epigenetic, environmental, and immunological factors. Of these contributing factors, non-coding RNAs (ncRNAs), including microRNAs (miRNAs, miRs), and long non-coding RNAs (lncRNAs) play critical roles in the post-transcriptional mRNA expression of cytokines, chemokines, and growth factors, which are essential for immune modulation. In the present review, we emphasize the roles of ncRNA expression in the immune-related cells and cell-free plasma, urine, and tissues contributing to the immunopathogenesis and tissue damage in SLE. In addition, the circular RNAs (circRNA) and their post-translational regulation of protein synthesis in SLE are also briefly described. We wish these critical reviews would be useful in the search for biomarkers/biosignatures and novel therapeutic strategies for SLE patients in the future.

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Epigenetic Mechanisms and Posttranslational Modifications in Systemic Lupus Erythematosus

Cited by 23 publications

References 79 publications

Classification of Systemic Lupus Erythematosus Using Raman Spectroscopy of Blood and Automated Computational Detection Methods: A Novel Tool for Future Diagnostic Testing

Classification of Systemic Lupus Erythematosus Using Raman Spectroscopy of Blood and Automated Computational Detection Methods: A Novel Tool for Future Diagnostic Testing

Advances in the potential roles of Cullin-RING ligases in regulating autoimmune diseases

Aberrant Non-Coding RNA Expression in Patients with Systemic Lupus Erythematosus: Consequences for Immune Dysfunctions and Tissue Damage

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