Intestinal Permeability and IgA Provoke Immune Vasculitis Linked to Cardiovascular Inflammation

Rivas, Magali Noval; Wakita, Daiko; Franklin, Michael; Carvalho, Thacyana T.; Abolhesn, Amanda; Gómez, Alejandro Raúl Gratacós; Fishbein, Michael C.; Chen, Shuang; Lehman, Thomas J. A.; Satoh, Kaneo; Shibuya, Akira; Fasano, Alessio; Kiyono, Hiroshi; Abe, Masanori; Tatsumoto, Narihito; Yamashita, M; Crother, Timothy R.; Shimada, Kenichi; Arditi, Moshe

doi:10.1016/j.immuni.2019.05.021

Cited by 106 publications

(79 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IL-1β is a key mediator in sepsis-induced inflammation and tissue injury (10,11,29). Macrophage-generated IL-1β acting through IL-1R1 during sepsis disrupted vascular stability (11,26).…”

Section: Discussionmentioning

confidence: 99%

IL-1β suppression of VE-cadherin transcription underlies sepsis-induced inflammatory lung injury

Xiong

Hong

Huang

et al. 2020

Journal of Clinical Investigation

133

View full text Add to dashboard Cite

“…IL-1β is a key mediator in sepsis-induced inflammation and tissue injury (10,11,29). Macrophage-generated IL-1β acting through IL-1R1 during sepsis disrupted vascular stability (11,26).…”

Section: Discussionmentioning

confidence: 99%

IL-1β suppression of VE-cadherin transcription underlies sepsis-induced inflammatory lung injury

Xiong

Hong

Huang

et al. 2020

Journal of Clinical Investigation

133

View full text Add to dashboard Cite

“…include cardiovascular and lung disorders, diabetes, and cancer. 65 Many of the specific medical conditions that are included within these groups of disorders are linked to an elevation in gut dysbiosis/ permeability, 66,67 mitochondrial dysfunction, 68 and circadian dysregulation, 69,70 with melatonin showing utility in their management. 71,72 Ageing, the main risk factor for death from influenza and covid-19, is highly associated with these pathophysiological changes, [73][74][75][76] with melatonin, partly via sirtuin induction as well as circadian and mitochondria regulation, attenuating ageing-associated processes.…”

Section: Preexisting Medical Conditionsmentioning

confidence: 99%

Melatonin: Roles in influenza, Covid‐19, and other viral infections

Anderson¹,

Reíter

2020

Reviews in Medical Virology

182

173

View full text Add to dashboard Cite

There is a growing appreciation that the regulation of the melatonergic pathways, both pineal and systemic, may be an important aspect in how viruses drive the cellular changes that underpin their control of cellular function. We review the melatonergic pathway role in viral infections, emphasizing influenza and covid-19 infections. Viral, or preexistent, suppression of pineal melatonin disinhibits neutrophil attraction, thereby contributing to an initial "cytokine storm", as well as the regulation of other immune cells. Melatonin induces the circadian gene, Bmal1, which disinhibits the pyruvate dehydrogenase complex (PDC), countering viral inhibition of Bmal1/PDC. PDC drives mitochondrial conversion of pyruvate to acetyl-coenzyme A (acetyl-CoA), thereby increasing the tricarboxylic acid cycle, oxidative phosphorylation, and ATP production. Pineal melatonin suppression attenuates this, preventing the circadian "resetting" of mitochondrial metabolism. This is especially relevant in immune cells, where shifting metabolism from glycolytic to oxidative phosphorylation, switches cells from reactive to quiescent phenotypes. Acetyl-CoA is a necessary cosubstrate for arylalkylamine N-acetyltransferase, providing an acetyl group to serotonin, and thereby initiating the melatonergic pathway. Consequently, pineal melatonin regulates mitochondrial melatonin and immune cell phenotype. Virus-and cytokinestorm-driven control of the pineal and mitochondrial melatonergic pathway therefore regulates immune responses. Virus-and cytokine storm-driven changes also increase gut permeability and dysbiosis, thereby suppressing levels of the short-chain fatty acid, butyrate, and increasing circulating lipopolysaccharide (LPS). The alterations in butyrate and LPS can promote viral replication and host symptom severity via impacts on the melatonergic pathway. Focussing on immune regulators has treatment implications for covid-19 and other viral infections.

show abstract

“…These results might support the hypothesis of the Kawasaki disease that occurred coincidentally during HSP. In contrast, Noval Rivas et al [22] showed that strong evidence that intestinal IgA production is increased during the acute phase of Kawasaki disease in human patients and in a murine model of Kawasaki disease vasculitis. Moreover, they showed that intestinal epithelial barrier dysfunction in this model results in sIgA leakage and sIgA-C3 complex deposition in to vascular tissues and glomeruli.…”

Section: Discussionmentioning

confidence: 94%

“…Moreover, they showed that intestinal epithelial barrier dysfunction in this model results in sIgA leakage and sIgA-C3 complex deposition in to vascular tissues and glomeruli. They concluded that these data suggest that Kawasaki disease may be a form of IgA vasculitis [22].…”

Section: Discussionmentioning

confidence: 99%

Myocarditis and intracardiac thrombus due to Henoch-Schönlein purpura: case report and literature review

et al. 2020

View full text Add to dashboard Cite

Cardiac involvement is very rare in patients with Henoch-Schönlein purpura (HSP). In this case study, we present an 8-year-old girl presenting with HSP-induced myocarditis and thrombus in the right atrium and HSP nephritis. To date, 15 cases of HSPrelated cardiac involvement have been reported in the PubMed/MEDLINE, Scopus, and Google Scholar databases. These cases, together with our case, are included in this review. We excluded those patients with other rheumatologic diseases (acute rheumatic fever, acute post-streptococcal glomerulonephritis, Kawasaki disease) accompanied by HSP. Three were children and 13 were adults and all were male except our case. This review revealed tachyarrhythmia, chest pain, dyspnea, murmur, and heart failure as the major signs. Cardiac tests, electrocardiogram (ECG), and imaging methods (echocardiography in all patients, cardiac magnetic resonance imaging (MRI) in three, cardiac biopsy in one, and post-mortem necropsy in three) showed that the cardiac involvements were pericardial effusion, intra-atrial thrombus, myocarditis, coronary artery changes, myocardial ischemia, infarction and necrosis, subendocardial hemorrhage, and left ventricular dilatation. Kidney involvement was not observed in three patients. As the treatment, high-dose prednisolone and cyclophosphamide, oral corticosteroid, azathioprine, nadroparin calcium, ACE inhibitors, calcium antagonists, beta-blockers, and diuretics were used. Eleven patients (all three children and eight of the adults) had a complete cardiac recovery. Cardiac involvement in adults was more likely to be fatal. Death (three patients), ischemia, and infarct have been reported only in adults. We suggested that early and aggressive treatment can be life-saving. MRI examination is effective at identifying cardiac involvement.

show abstract

Intestinal Permeability and IgA Provoke Immune Vasculitis Linked to Cardiovascular Inflammation

Cited by 106 publications

References 67 publications

IL-1β suppression of VE-cadherin transcription underlies sepsis-induced inflammatory lung injury

IL-1β suppression of VE-cadherin transcription underlies sepsis-induced inflammatory lung injury

Melatonin: Roles in influenza, Covid‐19, and other viral infections

Myocarditis and intracardiac thrombus due to Henoch-Schönlein purpura: case report and literature review

Contact Info

Product

Resources

About