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Precise Lipidomics Decipher Circulating Ceramide and Sphingomyelin Cycle Associated with the Progression of

Hemi Luan1, Shuailong Chen2, Longshan Zhao2

  • 1Department of Biomedical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, Guangdong 510006, China.

Journal of Proteome Research
|October 26, 2023
PubMed

Insights

Researchers found that specific ceramides and sphingomyelin (SM) cycles are linked to rheumatoid arthritis (RA) progression. Targeting these lipid pathways, particularly involving SMPD3, may offer new therapeutic strategies for RA patients.

Area of Science:

  • Biochemistry
  • Immunology
  • Rheumatology

Background:

  • Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation.
  • Lipid mediators play a role in RA pathogenesis and joint damage.
  • Current therapeutic targets for RA related to lipid metabolism have shown limited success.

Purpose of the Study:

  • To investigate the role of serum ceramides and sphingomyelin (SM) in rheumatoid arthritis.
  • To identify novel diagnostic biomarkers for RA, including antibody-negative RA.
  • To explore potential therapeutic targets within the ceramide/SM metabolic cycle.

Main Methods:

  • Utilized precise lipidomic technology to quantify serum ceramides and SM in a large patient cohort.
  • Analyzed the correlation between specific lipid species and RA activity.
  • Investigated the role of sphingomyelin phosphodiesterase 3 (SMPD3) in RA pathogenesis.

Main Results:

  • Identified an association between accumulating circulating ceramides and disrupted ceramide/SM cycles in RA progression.
  • Found that eight ceramides positively correlate with RA activity, improving diagnostic accuracy, especially in antibody-negative RA.
  • Demonstrated that SMPD3 disrupts the SM cycle, accelerating RA, and that methotrexate inhibits SMPD3 activity.

Conclusions:

  • Disturbed ceramide/SM cycles are implicated in rheumatoid arthritis.
  • Specific ceramides can serve as biomarkers for RA diagnosis and activity.
  • Targeting the SM cycle, potentially via SMPD3 inhibition, represents a promising therapeutic avenue for RA.
Keywords:
ceramidelipidomicsrheumatoid arthritissphingomyelin

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