Secretory sphingomyelinase (S-SMase) activity is elevated in patients with rheumatoid arthritis

Abstract

Objective The goals of this study were to determine if secretory sphingomyelinase (S-Smase) activity is elevated in patients with rheumatoid arthritis (RA) compared to control subjects, and to examine the relationships of S-Smase activity with functional status, quality of life and RA disease activity measurements. Methods We collected data on 33 patients who were diagnosed with RA and 17 non- RA controls who were comparable in terms of age, sex and race. Demographic, clinical data and self-reported measures of fatigue, pain and physical function were obtained directly from patients and controls. RA patients also completed quantitative joint assessment using a 28-joint count and functional status and quality of life assessment using the Modified Health Assessment Questionnaire (mHAQ). Archived serum samples were used to analyze retrospectively serum S-SMase activity in patients and controls. Results The mean serum S-SMase activity was 1.4-fold higher in patients with RA (RA: 2.8 ± 1.0 nmol/mL/hr vs. Controls: 2.0 ± 0.8 nmol/mL/hr; p=0.014). Spearman’s rho correlations between S-Smase activity and oxidant activity, markers of inflammation and endothelial activation with the exception of P-selectin (rho=0.40, p=0.034), measures of disease activity, functional status and quality of life were not statistically significant in patients with RA. Conclusion We confirmed S-SMase activity is higher among RA patients compared to controls, as in other acute and chronic inflammatory diseases. Future studies can build on the present findings to understand more fully the biologic role(s) of S-SMase activity in RA.

Keep Your Friends Close, but Your Enemies Closer: Role of Acid Sphingomyelinase During Infection and Host Response

“…A further increase was associated with greater risk by the severity of illness and with fatal outcome (34). Supporting the hypothesis that ASM activity is highly correlated to inflammation, we also found ASM activity mildly increased in patients with rheumatoid arthritis, which was associated with oxidant activity, markers of inflammation, and endothelial activation (129). Interestingly, treatment of these patients by biologicals with TNF-α-binding capacity suppressed the increase completely to levels as found in healthy controls along with improvement of the clinical condition (130).…”

Increased monohexosylceramide levels in the serum of established rheumatoid arthritis patients

“…In an arthritic rat model, serum Cer, HexCer, So and S1P were up-regulated, while sphingomyelins were down-regulated when compared with the respective control animal group [15]. In addition, higher activity of the serum secretory sphingomyelinase (S-SMase) enzyme was reported in patients with RA [16]. S-SMase is an extracellular member of sphingomyelinases, enzymes that hydrolyze sphingomyelin to Cer, and activation of SMases is pivotal for ceramide production during inflammation [16].…”

“…In addition, higher activity of the serum secretory sphingomyelinase (S-SMase) enzyme was reported in patients with RA [16]. S-SMase is an extracellular member of sphingomyelinases, enzymes that hydrolyze sphingomyelin to Cer, and activation of SMases is pivotal for ceramide production during inflammation [16].…”

Study on the potential mechanism of the active components in YiYiFuZi powder in homotherapy for hetropathy of coronary heart disease and rheumatoid arthritis

“…These findings suggest that ASM is a key target for the treatment of related diseases, and ASM enzyme activity has been found to be significantly higher in patients with cardiovascular disease, diabetes, or major depression than in normal subjects (Yang et al, 2018). In RA clinical studies, the mean serum S-SMase activity was twofold higher in RA patients than in normal controls (Hanaoka et al, 2017).…”

“…These findings suggest that ASM is a key target for the treatment of related diseases, and ASM enzyme activity has been found to be significantly higher in patients with cardiovascular disease, diabetes, or major depression than in normal subjects ( Yang et al, 2018 ). In RA clinical studies, the mean serum S-SMase activity was twofold higher in RA patients than in normal controls ( Hanaoka et al, 2017 ). In addition, the ASM enzyme was analyzed in a mouse model of inflammatory arthritis by ASM knockdown as well as amitriptyline treatment for significant backregulation of joint swelling and proinflammatory cytokine levels in joint inflammation ( Beckmann et al, 2017 ).…”