DNA-damaging autoantibodies and cancer: the lupus butterfly theory

Noble, Philip W.; Bernatsky, Sasha; Clarke, Ann E.; Isenberg, David; Ramsey‐Goldman, Rosalind; Hansen, James E.

doi:10.1038/nrrheum.2016.23

Cited by 74 publications

(71 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RA affects all populations, although it is much more prevalent in some groups (e.g., 5-6% in some Native American groups) and much less prevalent in others (e.g., black persons from the Caribbean region) [193]. SLE can be defined as a chronic inflammatory and autoimmune disease that can affect multiple organ systems, including skin, joints, kidneys, and the brain, among others [194]. SLE is characterized by a deposition of immune complexes, which are formed in large amounts as antinuclear antibodies bind to the abundant nuclear material in blood and tissues, along with disturbances in both innate and adaptive immunity and T-cell signaling.…”

Section: Secoiridoids Olive Tree In Autoimmune Diseasesmentioning

confidence: 99%

Potential Protective Role Exerted by Secoiridoids from Olea europaea L. in Cancer, Cardiovascular, Neurodegenerative, Aging-Related, and Immunoinflammatory Diseases

et al. 2020

View full text Add to dashboard Cite

Iridoids, which have beneficial health properties, include a wide group of cyclopentane [c] pyran monoterpenoids present in plants and insects. The cleavage of the cyclopentane ring leads to secoiridoids. Mainly, secoiridoids have shown a variety of pharmacological effects including anti-diabetic, antioxidant, anti-inflammatory, immunosuppressive, neuroprotective, anti-cancer, and anti-obesity, which increase the interest of studying these types of bioactive compounds in depth. Secoiridoids are thoroughly distributed in several families of plants such as Oleaceae, Valerianaceae, Gentianaceae and Pedialaceae, among others. Specifically, Olea europaea L. (Oleaceae) is rich in oleuropein (OL), dimethyl-OL, and ligstroside secoiridoids, and their hydrolysis derivatives are mostly OL-aglycone, oleocanthal (OLE), oleacein (OLA), elenolate, oleoside-11-methyl ester, elenoic acid, hydroxytyrosol (HTy), and tyrosol (Ty). These compounds have proved their efficacy in the management of diabetes, cardiovascular and neurodegenerative disorders, cancer, and viral and microbial infections. Particularly, the antioxidant, anti-inflammatory, and immunomodulatory properties of secoiridoids from the olive tree (Olea europaea L. (Oleaceae)) have been suggested as a potential application in a large number of inflammatory and reactive oxygen species (ROS)-mediated diseases. Thus, the purpose of this review is to summarize recent advances in the protective role of secoiridoids derived from the olive tree (preclinical studies and clinical trials) in diseases with an important pathogenic contribution of oxidative and peroxidative stress and damage, focusing on their plausible mechanisms of the action involved.

show abstract

Section: Secoiridoids Olive Tree In Autoimmune Diseasesmentioning

confidence: 99%

Potential Protective Role Exerted by Secoiridoids from Olea europaea L. in Cancer, Cardiovascular, Neurodegenerative, Aging-Related, and Immunoinflammatory Diseases

et al. 2020

View full text Add to dashboard Cite

show abstract

“…One study reported that SLE patients have a more condensed chromatin structure that leads to downregulation of genes that function in NER and HDR and defective DNA repair [34]. Recent work has also provided evidence for the existence of lupus autoantibodies that recognize DNA repair proteins and that are able to enter into the nucleus and inhibit DNA repair (for a review see [35]).…”

Section: Genetics Of Dna Repair and Lupusmentioning

confidence: 99%

DNA repair and systemic lupus erythematosus

2017

View full text Add to dashboard Cite

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with no known cure that affects at least five million people worldwide. Monozygotic twin concordance and familial aggregation studies strongly suggest that lupus results from genetic predisposition along with environmental exposures including UV light. The majority of the common risk alleles associated with genetic predisposition to SLE map to genes associated with the immune system. However, evidence is emerging that implicates a role for aberrant DNA repair in the development of lupus. Here we summarize our current knowledge of the potential association of lupus with mutations in DNA repair genes. We also discuss how defective or aberrant DNA repair could lead to the development of lupus.

show abstract

“…The anti-dsDNA autoantibody is the critical factor in the pathogenesis of SLE [15]. The level of anti-dsDNA antibodies in serum and anti-dsDNA antibodies deposition in the glomeruli absolutely correlate with lupus nephritis progress in SLE patients [16].…”

Section: Resultsmentioning

confidence: 99%

The Systemic Activation of Programmed Death 1-PD-L1 Axis Protects Systemic Lupus Erythematosus Model from Nephritis

Liao

Zheng²,

Wu³

et al. 2017

Am J Nephrol

View full text Add to dashboard Cite

Background: Systemic lupus erythematosus (SLE) is characterized by abnormal activated T cells, autoreactive B cells, and massive cytokines. The CD4+ T cells determined B-cells differentiation and cytokines production. The programmed death 1 (PD-1) is the checkpoint immunoinhibitory receptor of activated T cells, and its engagement could exhaust T cells. In this study, we investigated the role of PD-1 systemic engagement with PD-L1-Ig in lupus-like nephritis in SLE mice. Methods: The murine PD-L1-Ig was injected into SLE-prone mice. The proteinuria and survival ratio were monitored. The production of anti-dsDNA autoantibodies and cytokines in serum were measured by enzyme-linked immunosorbent assay. The cytokine-producing T cells (interferon-γ, IFN-γ and IL-17α) in kidney and spleen were detected with flowcytometry. The pathological evaluation of the Ig deposition in the glomeruliand was determined with immunofluorescence. Lymphocytes in 24-h urine were detected with flowcytometry. Results: The systemic administration of PD-L1-Ig activated PD-1-PD-L1 axis of CD4+ T lymphocytes, suppressed Th17 formation in many organs, including the spleen and the kidney, demolished abnormal production of cytokines (IFN-γ, IL-17, and IL-10) and anti-dsDNA autoantibodies in serum, inhibited immunoglobulin G deposition in the glomeruli with the decrease of proteinuria, and activated T cells in urine. Accordingly, the systemic conjugation of PD-L1-PD-1 impaired renal autoimmune injure and prolonged survival time. Conclusion: Our research demonstrated that the protective function of systemic activation of PD-1-PD-L1 axis with PD-L1-Ig attenuates the nephritis in SLE-prone mice, which facilitates us to understand the suppressive function of PD-1-PD-L1 axis in the pathogenesis and progress of the lupus nephritis, and to explore a possible effective therapeutic strategy to SLE.

show abstract

DNA-damaging autoantibodies and cancer: the lupus butterfly theory

Cited by 74 publications

References 67 publications

Potential Protective Role Exerted by Secoiridoids from Olea europaea L. in Cancer, Cardiovascular, Neurodegenerative, Aging-Related, and Immunoinflammatory Diseases

Potential Protective Role Exerted by Secoiridoids from Olea europaea L. in Cancer, Cardiovascular, Neurodegenerative, Aging-Related, and Immunoinflammatory Diseases

DNA repair and systemic lupus erythematosus

The Systemic Activation of Programmed Death 1-PD-L1 Axis Protects Systemic Lupus Erythematosus Model from Nephritis

Contact Info

Product

Resources

About