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THU0324 Neutrophils in giant cell arteritis: monitoring disease progression during therapy tapering
  1. T Kuret1,
  2. K Lakota1,2,
  3. P Žigon1,
  4. M Ogrič1,
  5. Ž Rotar1,
  6. R Ješe1,
  7. S Sodin-Šemrl1,2,
  8. S Čučnik1,3,
  9. M Tomšič1,4,
  10. A Hočevar1
  1. 1Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana
  2. 2FAMNIT, University of Primorska, Koper
  3. 3Faculty of Pharmacy
  4. 4Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

Abstract

Background Giant Cell Arteritis (GCA) represents a medical emergency due to risk of permanent vision loss and/or cerebrovascular insults. Polymyalgia rheumatic (PMR) frequently coexists with GCA1. No diagnostic or prognostic markers are yet known for GCA and predicting relapses during steroid therapy tapering is difficult. Biomarkers, such as serum amyloid A (SAA) and interleukin-6 (IL-6) provide added value for monitoring inflammation and a recent investigational study indicated the potential use of neutrophils and their surface markers in GCA pathogenesis2.

Objectives To determine the percentage of neutrophils, T and B cells, and the mean fluorescence intensity (MFI) of L-selectin (CD62L) and integrin αM (CD11b) on CD16+ neutrophils in peripheral blood of newly diagnosed, untreated GCA and PMR patients vs. healthy controls (time 0) and at GCA follow-up (7, 30 and 90 days after therapy).

Methods Flow cytometry of stained, lysed and fixed whole blood2 was performed in 10 GCA patients (6 followed longitudinally), 7 PMR patients and 5 healthy controls (7-colour immunophenotyping kit, Miltenyi). Levels of SAA and IL-6 were measured in sera of GCA patients (n=6) using nephelometry and ELISA, respectively.

Results Percentage of neutrophils was significantly higher at time 0 in GCA and PMR patients compared to healthy controls. Expression of both CD62L and CD11b on CD16+ neutrophils was also higher in GCA and PMR patients, as compared to healthy controls. Longitudinally, GCA patients showed an initial decrease in percentage of neutrophils at day 7 in comparison with time 0, increasing on days 30 and 90, while both T (CD4+) and B cells exhibited a significant elevation in % at day 7, with a decline at days 30 and 90. The MFI of neutrophil CD62L steadily decreased from day 0 (85.80±45.45) to day 7 (71.99±29.93) and day 30 (57.61±42.17), while showing a substantial increase on day 90 (88.54±60.35). CD11b expression diminished initially and remained reduced on day 90. Levels of SAA and IL-6 declined sharply from day 0 to 7 (>10-fold drop) and day 30, with gradual elevation of both on day 90.

Conclusions Neutrophil CD62L may represent a good surface marker for monitoring disease progression following glucocorticoid tapering. SAA and IL-6 exhibit a sharp decrease at early time points, increasing at day 90. In the future, a larger, longer study of neutrophils and their CD62L expression could support clinicians in their decision when and how to re-evaluate therapy in GCA patients.

References

  1. Schmidt J, Warrington KJ. Polymyalgia rheumatica and giant cell arteritis in older patients: diagnosis and pharmacological management. Drugs & aging. 2011;28651–66.

  2. Nadkarni S et al. Investigational analysis reveals a potential role for neutrophils in GCA disease progression. Circ.Res. 2014;114:242–48.

References

Disclosure of Interest None declared

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