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Elevated active secretory sphingomyelinase in antineutrophil cytoplasmic antibody-associated primary systemic vasculitis
  1. Allan P Kiprianos1,
  2. Matthew D Morgan2,
  3. Mark A Little3,
  4. Lorraine Harper2,
  5. Paul A Bacon1,
  6. Stephen P Young1
  1. 1Rheumatology Research Group, University of Birmingham, School of Immunity & Infection, College of Medical and Dental Sciences, Birmingham, UK
  2. 2Renal Immunobiology, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
  3. 3University College London, Centre for Nephrology Royal Free Hospital, London, NW3 2PF, UK
  1. Correspondence to Dr Stephen P Young, Rheumatology Research Group, University of Birmingham, School of Immunity & Infection, College of Medical and Dental Sciences, Birmingham B15 2TT, UK; s.p.young{at}

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Endothelial cell (EC) dysfunction (ECD) occurs in antineutrophil cytoplasmic antibody-associated systemic vasculitis (AASV)1 2 but improves with anti-tumour necrosis factor α (anti-TNFα) treatment,1 suggesting a key role for this cytokine. TNFα and interleukin 1 can induce secretion of acid sphingomyelinase (ASM) from ECs,3 4 which are the major source of this enzyme. ASM potently depresses calcium signals in lymphocytes5 and in EC (Church et al, unpublished observations). We hypothesised that endothelial inflammation in AASV would raise circulating levels of secretory sphingomyelinase (S-SMase), perpetuating vascular dysfunction.

Plasma from 18 patients with active AASV undergoing plasmapheresis (15 men, 3 women) were compared with 7 inflammatory renal disease controls and 9 healthy individuals. Sera were also collected from 20 AASV patients (9 women and 11 men) during active disease, after 14 weeks of immunosuppressive therapy and from patients in established remission on low-dose immunosuppression (6 months; n=7). Activity was assessed with the Birmingham vasculitis activity score (BVAS).6 S-SMase activity was assayed by hydrolysis of 6-((N-(7-nitrobenz- 2-oxa-1,3-diazol-4-yl)amino) hexanoyl)sphingosylphosphocholine (NBD C6-sphingomyelin)7 and the protein detected using immunoblotting following immunoprecipitation with an anti-ASM antibody (Santa-Cruz Biotechnology, Santa Cruz, CA, United States).

Plasma S-SMase activity was raised in patients with …

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  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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