Elevated active secretory sphingomyelinase in antineutrophil cytoplasmic antibody-associated primary systemic vasculitis

Kiprianos, Allan; Morgan, Matthew D.; Little, Mark A.; Harper, Lorraine; Bacon, P. A.; Young, Stephen P.

doi:10.1136/annrheumdis-2011-200445

Cited by 5 publications

(8 citation statements)

References 10 publications

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“…SIRS, systemic inflammatory response syndrome; NPD, Niemann-Pick disease. Literature (in alphabetical order of the description in the Figure): acute myocardial infarction (Pan et al, 2014), alcohol detoxification , allergy ), Alzheimer's disease (Lee et al, 2014), chronic heart failure (Pan et al, 2014), diabetes mellitus II (Górska et al, 2003), hepatitis C (Grammatikos et al, 2014), inflammatory renal disease (Kiprianos et al, 2012), lymphohistiocytosis (Takahashi et al, 2002;Jenkins et al, 2013), non-alcoholic fatty liver (Grammatikos et al, 2014), NPD-B (Abe et al, 1999;He et al, 2003), NPD-B carrier (He et al, 2003), post-operative (Kott et al, 2014), post-traumatic stress disorder , rs1050239 , rs141641266 (Rhein et al, 2013), sepsis (Claus et al, 2005), signal peptide repeat 4/4 , SIRS (Kott et al, 2014), stable angina pectoris (Pan et al, 2014), systemic vasculitis ( Kiprianos et al, 2012), unstable angina pectoris (Pan et al, 2014), and Wilson disease (Lang et al, 2007).…”

Section: Pharmacologymentioning

confidence: 99%

“…Mildly elevated activities are observed in Alzheimer's disease (Lee et al, 2014), type II diabetes mellitus (Górska et al, 2003), stable angina pectoris, acute myocardial infarction (Pan et al, 2014), chronic heart failure (Doehner et al, 2007), post-traumatic stress disorder and in response to ionizing radiation treatment in cancer patients (Sathishkumar et al, 2005). Marked increases in activity ( > 200%) are observed in unstable angina pectoris (Pan et al, 2014), Wilson disease (Lang et al, 2007), sepsis (Claus et al, 2005), systemic inflammatory response syndrome (Kott et al, 2014), lymphohistiocytosis (Takahashi et al, 2002;Jenkins et al, 2013), non-alcoholic fatty liver, hepatitis C (Grammatikos et al, 2014), systemic vasculitis, inflammatory renal disease (Kiprianos et al, 2012) and in patients with alcohol dependency undergoing withdrawal . In sepsis, lymphohistiocytosis, systemic inflammatory response syndrome and chronic heart failure, high S-ASM activity is associated with higher mortality (Claus et al, 2005;Doehner et al, 2007;Jenkins et al, 2013;Kott et al, 2014).…”

Section: Cross-sectional Clinical Studiesmentioning

confidence: 99%

“…In contrast to a pronounced decrease in C-reactive protein (CRP), S-ASM activity only normalizes to a minor extent within 2 weeks in patients with systemic vasculitis undergoing immunosuppressive therapy, resulting in a dissociation of S-ASM activity and CRP-levels during the treatment of these patients (Kiprianos et al, 2012). Increased S-ASM activity was measured at baseline in male alcohol-dependent patients entering an alcohol withdrawal program.…”

Section: Longitudinal Clinical Studiesmentioning

confidence: 99%

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Secretory sphingomyelinase in health and disease

Kornhuber

Rhein

Müller

et al. 2015

Biological Chemistry

124

138

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Acid sphingomyelinase (ASM), a key enzyme in sphingolipid metabolism, hydrolyzes sphingomyelin to ceramide and phosphorylcholine. In mammals, the expression of a single gene, SMPD1, results in two forms of the enzyme that differ in several characteristics. Lysosomal ASM (L-ASM) is located within the lysosome, requires no additional Zn 2+ ions for activation and is glycosylated mainly with high-mannose oligosaccharides. By contrast, the secretory ASM (S-ASM) is located extracellularly, requires Zn 2+ ions for activation, has a complex glycosylation pattern and has a longer in vivo half-life. In this review, we summarize current knowledge regarding the physiology and pathophysiology of S-ASM, including its sources and distribution, molecular and cellular mechanisms of generation and regulation and relevant in vitro and in vivo studies. Polymorphisms or mutations of SMPD1 lead to decreased S-ASM activity, as detected in patients with Niemann-Pick disease B. Thus, lower serum/ plasma activities of S-ASM are trait markers. No genetic causes of increased S-ASM activity have been identified. Instead, elevated activity is the result of enhanced release (e.g., induced by lipopolysaccharide and cytokine stimulation) or increased enzyme activation (e.g., induced by oxidative stress). Increased S-ASM activity in serum or plasma is a state marker of a wide range of diseases. In particular, high S-ASM activity occurs in inflammation of the endothelium and liver. Several studies have demonstrated a correlation between S-ASM activity and mortality induced by severe inflammatory diseases. Serial measurements of S-ASM reveal prolonged activation and, therefore, the measurement of this enzyme may also provide information on past inflammatory processes. Thus, S-ASM may be both a promising clinical chemistry marker and a therapeutic target.

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Section: Pharmacologymentioning

confidence: 99%

Section: Cross-sectional Clinical Studiesmentioning

confidence: 99%

Section: Longitudinal Clinical Studiesmentioning

confidence: 99%

See 1 more Smart Citation

Secretory sphingomyelinase in health and disease

Kornhuber

Rhein

Müller

et al. 2015

Biological Chemistry

124

138

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“…Mild elevations of blood S-ASM activity were observed in Alzheimer's disease (Lee et al 2014), type 2 diabetes mellitus (Górska et al 2003), stable angina pectoris (Pan et al 2014), acute myocardial infarction (Pan et al 2014), chronic heart failure (Doehner et al 2007), post-traumatic stress disorder (Hammad et al 2012), and in response to ionizing radiation treatment in cancer patients (Sathishkumar et al 2005). Marked elevations of blood S-ASM activity were observed in unstable angina pectoris (Pan et al 2014), Wilson disease (Lang et al 2007), sepsis (Claus et al 2005), systemic inflammatory response syndrome (Kott et al 2014), lymphohistiocytosis (Takahashi et al 2002;Jenkins et al 2013), non-alcoholic fatty liver (Grammatikos et al 2014), hepatitis C (Grammatikos et al 2014), systemic vasculitis inflammatory renal disease (Kiprianos et al 2012), and in patients with alcohol dependency undergoing withdrawal . Thus, ASM has a potential pathophysiological role in these diseases.…”

Section: +mentioning

confidence: 99%

Elevation of Serum Acid Sphingomyelinase Activity in Children with Acute Respiratory Syncytial Virus Bronchiolitis

Yoshida

Noguchi

Kikuchi³

et al. 2017

Tohoku J. Exp. Med.

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Acid sphingomyelinase (ASM) is a lysosomal enzyme that hydrolyzes sphingomyelin into ceramide, a bioactive lipid to regulate cellular physiological functions. Thus, ASM activation has been reported as a key event in pathophysiological reactions including inflammation, cytokine release, oxidative stress, and endothelial damage in human diseases. Since ASM activation is associated with extracellular ASM secretion through unknown mechanisms, it can be detected by recognizing the elevation of secretory ASM (S-ASM) activity. Serum S-ASM activity has been reported to increase in chronic diseases, acute cardiac diseases, and systemic inflammatory diseases. However, the serum S-ASM has not been investigated in common acute illness. This study was designed to evaluate serum S-ASM activity in children with common acute illness. Fifty children with common acute illness and five healthy children were included in this study. The patients were categorized into five groups based on clinical diagnoses: acute respiratory syncytial virus (RSV) bronchiolitis, adenovirus infection, streptococcal infection, asthma, and other infections due to unknown origin. The serum S-ASM activity was significantly elevated at 6.9 ± 1.6 nmol/0.1 mL/6 h in the group of acute RSV bronchiolitis patients compared with healthy children who had a mean level of 1.8 ± 0.8 nmol/0.1 mL/6 h (p < 0.05). In the other illness groups, the serum S-ASM activity was not significantly elevated. The results suggest an association of ASM activation with RSV infection, a cause for common acute illness. This is the first report to describe the elevation of serum S-ASM activity in respiratory tract infection.

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“…Activation of ASM and a concomitant increase in ceramide concentrations can be induced by the stimulation of various receptors, including CD95 or those for tumor necrosis factor (TNF)-α, interleukin (IL)-1β or platelet-activating factor, or by cellular stress such as inflammation, infection, ischemia, radiation, oxidative stress, chemotherapeutic agents or cell wounding [3,4,5,6,7,8,9,10,11,12]. Increased ASM activity was observed in several human diseases such as chronic heart failure, type 2 diabetes, sepsis, peritonitis, hepatitis, hemophagocytic lymphohistiocytosis, antineutrophil cytoplasmic antibody-associated primary systemic vasculitis, neurodegeneration, depression and alcohol abuse [13,14,15,16,17,18,19,20,21,22,23]. A variety of small organic, drug-like compounds that functionally inhibit ASM are used in the therapy of human diseases [24,25,26].…”

Section: Introductionmentioning

confidence: 99%

The Common Acid Sphingomyelinase Polymorphism p.G508R is Associated with Self-Reported Allergy

Reichel

Richter‐Schmidinger

Mühle

et al. 2014

Cell Physiol Biochem

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Background: Acid sphingomyelinase (ASM) is a key regulator of ceramide-dependent signalling pathways. Among others, activation of ASM can be induced by CD95 or cytokine signalling and by cellular stress resulting from inflammation or infection. Increased ASM activity was observed in a variety of human diseases including inflammatory and neuropsychiatric disorders. We hypothesized that basal ASM activity might influence the susceptibility for common human diseases. Methods: The general health condition of 100 young people was assessed using a questionnaire. The ASM polymorphism rs1050239 (c.1522G>A; encoding p.G508R) was determined from genomic DNA. Activities of secretory (S-) and lysosomal (L-) ASM were measured in blood plasma and peripheral blood cells respectively. Results: The polymorphism rs1050239 was significantly associated with self-reported allergy (p=4.68×10^-4; adjusted p-value for multiple testing 0.007). Allergy was more prevalent in carriers of the minor A allele compared to non-carriers (p=0.00015; odds ratio=6.5, 95% CI 2.15-21.7). S-ASM activity was significantly associated with rs1050239 (p=5.3×10^-7) and decreased with the number of A alleles in a gene-dosage dependent manner. In allergic patients, S-ASM activity was moderately decreased (p=0.034). L-ASM activity was significantly lower in subjects homozygous for the minor A allele (p=0.025) but not different between allergic and non-allergic subjects (p=0.318). Conclusion: Our analysis provides evidence for an involvement of ASM in the pathophysiology of allergy, which is in line with previous reports addressing the role of sphingolipids in this disorder. Further studies should clarify the mechanism linking rs1050239 to allergy. The ASM pathway might be useful for predicting allergic disposition and disease course and as a therapeutic target.

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Elevated active secretory sphingomyelinase in antineutrophil cytoplasmic antibody-associated primary systemic vasculitis

Cited by 5 publications

References 10 publications

Secretory sphingomyelinase in health and disease

Secretory sphingomyelinase in health and disease

Elevation of Serum Acid Sphingomyelinase Activity in Children with Acute Respiratory Syncytial Virus Bronchiolitis

The Common Acid Sphingomyelinase Polymorphism p.G508R is Associated with Self-Reported Allergy

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