Polyamine patterns in plasma of patients with systemic lupus erythematosus and fever

Kim, H A; Lee, H S; Shin, Tae Hwan; Jung, Ju‐Yang; Baek, Woon Yi; Park, H J; Lee, G; Paik, Man‐Jeong; Suh, Chang‐Hee

doi:10.1177/0961203317751860

Cited by 31 publications

(20 citation statements)

References 34 publications

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“…Here, we highlight its critical role in IFN-related autoimmune diseases. Consistent with this, spermidine and spermine in plasma of patients with SLE and fever were found to be decreased (Kim et al, 2018).…”

Section: Discussionsupporting

confidence: 76%

Spermidine Suppresses Inflammatory DC Function by Activating the FOXO3 Pathway and Counteracts Autoimmunity

Ding

et al. 2020

iScience

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Dendritic cells (DCs) function is intimately linked to microenvironment and metabolism. Type I interferons (IFNs) condition dendritic cells to respond to weak self-signals, leading to autoimmunity. However, the metabolic adaption in the process is unclear. Here, we identified spermidine as a critical metabolite impacting the metabolic fitness of DC. First, dynamic metabolome screening indicated that spermidine decreased during IFN priming and following TLR7 ligand stimulation, accompanied by metabolic change from oxidative phosphorylation to glycolysis. Second, spermidine supplement restrained the glycolysis and prevented the overactivation of IFN-a primed DC both in vivo and in vitro. Third, mechanism study uncovered that the activity of FOXO3 adapted to the metabolic change, mediating the anti-inflammatory effect of spermidine. More importantly, addition of spermidine in vivo greatly alleviated the development of psoriasis-like symptom in mice. Thus, our studies revealed metabolic changes boosting DC responses and identified spermidine as a potential therapeutic agent for autoimmune diseases.

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Section: Discussionsupporting

confidence: 76%

Spermidine Suppresses Inflammatory DC Function by Activating the FOXO3 Pathway and Counteracts Autoimmunity

Ding

et al. 2020

iScience

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“…Moreover, increased polyamines may downregulate interleukin‐2 in RA . Recently, Kim et al reported that systemic lupus erythematosus (SLE) patients had decreased plasma SPD, SPM, and NSPD and increased plasma CAD levels. However, little is known about the relationship between polyamine metabolites and AITD.…”

Section: Introductionmentioning

confidence: 99%

Serum polyamine metabolic profile in autoimmune thyroid disease patients

Song

Shan

Mao

et al. 2019

Clinical Endocrinology

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Summary Objective Polyamines are indispensable polycations and play important physiological roles in living cells. Some polyamine metabolites have been associated with autoimmune disorders. The aims of this study were to profile polyamine metabolites in autoimmune thyroid disease (AITD) and predict whether polyamine metabolites are associated with thyroid hormone, thyroid autoantibodies or disease progression. Design, patients and measurements A total of 136 participants were recruited, including Graves’ disease (GD) (n = 36), Hashimoto's thyroiditis (HT) (n = 33) and thyroid autoantibody‐positive (pTAb) (n = 29) patients and 38 age‐ and sex‐matched healthy controls (HCs). Fourteen polyamine metabolites, including polyamine precursors, polyamines and polyamine catabolite, were measured by UFLC‐MS/MS Results Both GD and HT patients had higher L‐arginine, L‐ornithine, lysine and agmatine levels and lower putrescine, 1,3‐diaminopropane, spermine, N‐acetylputrescine levels than HCs. Some polyamine metabolite levels were different only in GD or HT patients compared to HCs: GD patients had significantly higher spermidine, N‐acetylspermidine and γ‐aminobutyric acid and lower cadaverine, whereas HT patients had significantly decreased N‐acetylspermine. Only spermine and N‐acetylspermine were significantly lower in pTAb than HCs. The spermine:spermidine ratio was significantly reduced in all AITD patients. In addition, spermine was negatively correlated with thyroid‐specific antibodies grade. N‐acetylspermidine might be a risk factor for pTAb progression to overt hypothyroidism. Conclusions Compared with the HCs, most metabolites of GD and HT showed similar patterns, suggesting the possibility of a common pathophysiological basis or metabolic pathway. Moreover, pTAb progression to overt hypothyroidism may be related to high N‐acetylspermidine. Thyroid autoimmunity was associated with low spermine.

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“…Treatment with 1% DFMO in water given to NZB/W mice (a lupus-prone model) reduced IgG and IgA levels in the mice and reduced spermidine and putrescine levels suggesting the inhibition of ODC as a promising avenue for SLE therapeutics [69]. As for SLE in humans, Kim et al reported differences in plasma polyamine levels of SLE patients compared to controls with SLE patients showing significant decreases in spermine, spermidine, acetylspermidine, and acetylcadaverine while there was an increase in cadaverine [70]. Thomas et al reported greater binding of SLE anti-DNA antibodies in the presence of spermine, suggesting a possible role of spermine in the autoantigen creation [71].…”

Section: Polyaminesmentioning

confidence: 99%

An Epigenetics-Based Hypothesis of Autoantigen Development in Systemic Lupus Erythematosus

Brooks

2020

Epigenomes

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Currently, we have a limited understanding of mechanisms leading to systemic lupus erythematosus, but we know that genetics, environmental factors, and epigenetics contribute to the disease. One common aspect of the various environmental triggers is that they can cause cellular stress. When extraordinary stress occurs, such as viral activation, a cell’s response can include increased nucleolar volume and activity to produce more machinery (e.g., ribosomes) to help the cell recover. However, nucleolar expansion can disrupt the epigenetic control in neighboring heterochromatin that comprises the nucleolar shell. This disruption can open underlying vulnerabilities that provoke an autoimmune reaction. Here, we review the “X chromosome-nucleolus nexus” hypothesis, which explains how nucleolar stress can disrupt epigenetically silenced chromatin, especially the neighboring inactive X chromosome (aka the nucleolar satellite). Chromatin disruption can lead to the expression of sequestered DNA, such as Alu elements and fully functional LINE-1 reverse transcriptase genes. In addition, Alu transcripts can disrupt the nucleolar structural integrity, leading to nucleolar disintegration. Such disintegration can leave nucleolar components and products in autoantigenic forms, such as abnormal conformations or incomplete macromolecular assemblies. Recent research on DNA sensing pathways can now be incorporated into the hypothesis to provide further details explaining how autoantibodies to endogenous nucleic acids arise.

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Polyamine patterns in plasma of patients with systemic lupus erythematosus and fever

Cited by 31 publications

References 34 publications

Spermidine Suppresses Inflammatory DC Function by Activating the FOXO3 Pathway and Counteracts Autoimmunity

Spermidine Suppresses Inflammatory DC Function by Activating the FOXO3 Pathway and Counteracts Autoimmunity

Serum polyamine metabolic profile in autoimmune thyroid disease patients

An Epigenetics-Based Hypothesis of Autoantigen Development in Systemic Lupus Erythematosus

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