Autoimmune Disease-Associated Hypertension

Wolf, Victoria; Ryan, Michael J.

doi:10.1007/s11906-019-0914-2

Cited by 56 publications

(39 citation statements)

References 100 publications

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“…This therapy did not, however, alter disease progression as measured by anti-dsDNA antibody titers. These data are supported by numerous studies that suggest a role of ROS in the pathogenesis of SLE (12,25,41). The current study confirms an increase in superoxide production within monocytes of patients with SLE and supports a role of downstream isoLGs as a mechanism for systemic immune activation and hypertension in SLE.…”

Section: Discussionsupporting

confidence: 89%

“…(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Improvement in SLE associated renal injury and function with 2-HOBA: Patients with hypertension and SLE often exhibit abnormal sodium excretion and augmented albuminuria; moreover, glomerular injury secondary to immune complex deposition occurs in many patients with SLE (25,26). Using flow cytometry of single cell preparations of kidney homogenates, we observed a marked reduction in inflammation as evidenced by a reduction in renal CD45 + cells, CD3 + T cells, and CD4 + T cells in B6.SLE123 animals treated with 2-HOBA ( Figure 6 A-F).…”

Section: Sle-associated Hypertension Is Attenuated By 2-hobamentioning

confidence: 99%

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Isolevuglandins promote autoimmunity and hypertension in systemic lupus erythematosus

Visitación

et al. 2020

Preprint

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Hypertension, vascular inflammation and renal inflammation are characteristic of systemic lupus erythematosus (SLE), a multisystem autoimmune disease that is complex and poorly understood. Oxidation products of arachidonic and other fatty acids, termed isolevuglandins (isoLG) lead to formation of post-translational protein modifications that are immunogenic. We demonstrate isoLG enrichment in dendritic cells (DCs), B cells, and plasma cells from juvenile female B6.SLE123 mice. In adult B6.SLE123 and NZBWF1 mice, isoLG adducts are enriched in plasma cells and splenic DCs compared to C57Bl/6 and NZW mice respectively. Treatment with the isoLG-scavenger 2-hydroxybenzylamine (2-HOBA) reduced blood pressure, improved renal function, and attenuated renal injury. Moreover, 2-HOBA reduced bone marrow plasma cells, total IgG levels, and anti-dsDNA antibody titers. We also demonstrate that mice with SLE generate specific IgG antibodies against isoLG adducted protein, confirming the immunogenicity of isoLG adducts. Finally, we found that isoLG adducted peptides are markedly enriched in monocytes from patients with SLE which was accompanied by an increase in superoxide production. These findings support a role of isoLG adducts in the genesis and maintenance of systemic autoimmunity and its associated hypertension in SLE. Scavenging of isoLGs promises to be a novel therapy for this disease.

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Section: Discussionsupporting

confidence: 89%

Section: Sle-associated Hypertension Is Attenuated By 2-hobamentioning

confidence: 99%

Isolevuglandins promote autoimmunity and hypertension in systemic lupus erythematosus

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et al. 2020

Preprint

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“…Recent investigations have found a role of the immune system in hypertension [19–21]. Bilirubin modulates the immune response at several levels including modulation of regulatory T cells, modulation of T helper type 17 (Th17) cells, inactivation of the Nlrp3 inflammasome, and inhibition of the Toll-like receptor 4/nuclear factor kappaB signaling pathway [22–25].…”

Section: Bilirubin and Cardiorenal Protectionmentioning

confidence: 99%

Bilirubin Safeguards Cardiorenal and Metabolic Diseases: a Protective Role in Health

Hinds

Stec

2019

Curr Hypertens Rep

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Purpose of Review-To discuss recent advances indicating that bilirubin safeguards against cardiorenal and metabolic diseases. Recent Findings-Several investigations from human patient populations and experimental animal models have shown that bilirubin improves cardiorenal and metabolic dysfunction. The latest studies found an entirely new function of bilirubin suggesting that it acts as a hormone signaling molecule capable of activating nuclear receptors for burning fat, which may explain several of its protective actions. Summary-This review highlights the current findings (within the last 3 years) regarding cardiorenal and metabolic protective effects of bilirubin and the latest mechanism(s) that may be mediating these effects.

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“…However, a more extensive cohort study is needed to validate this hypothesis. Hypertension is prevalent in several autoimmune diseases, including SLE and RA promoting chronic inflammation [16]. Here, we speculate that hypertension may act as a risk factor promoting a pro-inflammatory environment, possibly leading to autoimmunity through bystander activation.…”

Section: Discussionmentioning

confidence: 86%

Detection of autoimmune antibodies in severe but not in moderate or asymptomatic COVID-19 patients

Fakhro¹,

Nasrallah

Khan

et al. 2021

Preprint

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The heterogeneity of COVID-19 lies within its diverse symptoms and severity, ranging from mild to lethal. Acute respiratory distress syndrome (ARDS) has been shown to be the leading cause of mortality in COVID-19 patients, characterized by a hyper cytokine storm. Autoimmunity is proposed to occur as a result of COVID-19, given the high similarity of the immune responses observed in COVID-19 and autoimmune diseases. Here, we investigate the level of autoimmune antibodies in COVID-19 patients with different severities. Initial screening for antinuclear antibodies (ANA) IgG revealed that 1.6% (2/126) and 4% (5/126) of ICU COVID-19 cases developed strong and moderate ANA levels, respectively. However, all the non-ICU cases (n=273) were ANA negative. The high ANA level was confirmed by immunofluorescence (IFA) and large-scale autoantibody screening by phage immunoprecipitation-sequencing (PhIP-Seq). Indeed, the majority of the samples showed "speckled" ANA pattern by microscopy, and we demonstrate that samples of ICU patients with strong and moderate ANA levels contain autoantibody specificities that predominantly targeted proteins involved in intracellular signal transduction, metabolism, apoptotic processes, and cell death; further denoting reactivity to nuclear and cytoplasmic antigens. In conclusion, our results further support the notion of routine screening for autoimmune responses in COVID-19 patients, which might help improve disease prognosis and patient management. Further, results provide compelling evidence that ANA-positive individuals should be excluded from being donors for convalescent plasma therapy in the context of Covid-19.

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Autoimmune Disease-Associated Hypertension

Cited by 56 publications

References 100 publications

Isolevuglandins promote autoimmunity and hypertension in systemic lupus erythematosus

Isolevuglandins promote autoimmunity and hypertension in systemic lupus erythematosus

Bilirubin Safeguards Cardiorenal and Metabolic Diseases: a Protective Role in Health

Detection of autoimmune antibodies in severe but not in moderate or asymptomatic COVID-19 patients

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