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P86 The NCF1–339 polymorphism is associated with altered formation of neutrophil extracellular traps, high serum interferon activity and antiphospholipid syndrome in systemic lupus erythematosus
  1. Sabine Arve1,
  2. Petrus Linge1,
  3. Lina Olsson2,
  4. Dag Leonard3,
  5. Christopher Sjöwall4,
  6. Martina Frodlund4,
  7. Iva Gunnarsson5,
  8. Elisabet Svenungsson5,
  9. Helena Tydén1,
  10. Andreas Jönsen1,
  11. Robin Kahn6,
  12. Åsa Johansson7,
  13. Lars Rönnblom3,
  14. Rikard Holmdahl2 and
  15. Anders Bengtsson1
  1. 1Dept. of Clinical Sciences, Rheumatology, Lund University, Lund
  2. 2Dept. of Medical Inflammation Research, Section of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm
  3. 3Dept. of Medical Sciences, Science for Life Laboratories, Rheumatology, Uppsala University, Uppsala
  4. 4Dept. of Clinical and Experimental Medicine, Rheumatology, Linköping University, Linköping
  5. 5Dept. of Medicine Solna, Rheumatology, Karolinska Institute and University Hospital, Stockholm
  6. 6Dept. of Clinical Sciences, Pediatrics, Lund University, Lund
  7. 7Dept. of Clinical Sciences, Hematology, Lund University, Lund, Sweden


Background A single nucleotide polymorphism in NCF1 (NCF1-339, rs201802880), encoding NADPH oxidase complex 2 subunit p47phox, reducing production of reactive oxygen species (ROS) is highly associated with development of systemic lupus erythematosus (SLE). However, the effect of NCF1-339 genotype on SLE regarding pathogenetic processes or comorbidities has not been investigated.

Methods NCF1-339 genotyped SLE subjects from four Swedish university hospitals were investigated regarding neutrophil ROS production (n=31), neutrophil extracellular traps (NETs) (n=31), serum interferon (n=141), autoantibody profiles (n=305) and clinical phenotypes (n=1087).

Results Compared to SLE patients with normal-ROS NCF1-339 genotypes, neutrophils from patients with low-ROS genotypes displayed impaired NET-formation and increased dependence on mitochondrial ROS for canonical NET-release. An increased frequency of low-ROS patients had high serum interferon activity. Patients with low-ROS genotypes had an increased frequency of positivity for antiphospholipid antibodies anti-β2 glycoprotein I and anti-cardiolipin, related to the severe comorbidity antiphospholipid syndrome (APS). No other autoantibodies investigated were associated with NCF1-339 genotype. Clinical characterization revealed a strong association between NCF1-339 low-ROS genotypes and secondary APS.

Conclusions NCF1-339 genotype affects neutrophil functions of ROS production, NET formation and dependence on mitochondrial ROS. SLE subjects with low-ROS NCF1-339 genotypes are associated with high serum interferon, presence of antiphospholipid antibodies and secondary APS.

Acknowledgements This study was primarily funded by FOREUM.

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