THU0465 A longitudinal study of neutrophil phenotype changes in giant cell arteritis
Authors: T. Kuret, K. Lakota, P. &Zcaron;igon, M. Ogri&ccaron;, S. Sodin-Šemrl, S. &Ccaron;u&ccaron;nik, M. Tomši&ccaron;, A. Ho&ccaron;evar
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Neutrophils with differential surface protein expression were recently implicated in pathogenesis of Giant Cell Arteritis (GCA)<sup>1</sup>. However, data are lacking with regard to treatment-naïve GCA and their long-term follow-up. <h3>Objectives</h3> To determine the expression of l-selectin (CD62L) and integrin αM (CD11b) on CD16<sup>+</sup> neutrophils in peripheral blood of newly diagnosed, treatment-naïve GCA cases, at the time of diagnosis (time 0) and during follow-up - at week 1, 4, 12, 24 and 48. In parallel, we aimed to measure also sera levels of serum amyloid A (SAA) and interleukin-6 (IL-6). <h3>Methods</h3> Peripheral blood from 33 treatment-naïve GCA patients and 16 healthy blood donors (HBD) was stained, lysed, fixed and analysed by flow cytometry (Miltenyi). SAA and IL-6 were measured by nephelometry and ELISA, respectively. 3/33 GCA patients experienced relapse and were analysed separately during follow-up, at the time of relapse and 12 weeks after relapse. At the time of diagnosis, all patients received steroid treatment and therapy tapering started after 4 weeks. At week 12, some of the patients (14/22) received leflunomide, in addition to steroid therapy. <h3>Results</h3> Expression of CD62L, but not CD11b, was significantly higher on CD16<sup>+</sup> neutrophils in treatment-naïve GCA patients (median; IQR: 72.5; 56.2–100.7), as compared to HBD (55.9; 44.5–70.6, p=0.017). Longitudinally, the expression of CD62L significantly decreased in GCA patients from day 0 to week 4 (p=0.005). At week 12 there was an elevation in CD62L which escalated also at week 24. Patients receiving steroids only showed a marked increase at week 48, while patients receiving also leflunomide exhibited a decrease (Fig 1). Expression of CD11b declined from day 0 to week 4, but substantially increased throughout weeks 12, 24 and 48, regardless of therapy used. SAA and IL-6 declined sharply from day 0 to week 1 and 4, with gradual elevation of both at week 12. There was a decline in SAA levels observed in all patients at week 24, while IL-6 increased in patients receiving only steroids. These patients exhibited further elevation of both markers at week 48, while patients receiving steroids, in combination with leflunomide, showed a decrease. In 2/3 patients who experienced a relapse, we could observe an increase in the expression of CD62L at the time of relapse, which was found to be decreased again 12 weeks later. A similar trend was observed for IL-6. <h3>Conclusions</h3> Neutrophil CD62L could represent a good surface marker for detection of relapse in GCA. A distinct dichotomy was found for CD62L, as well as SAA and IL-6 in GCA during long term follow-up, with the combination of steroids with leflunomide showing more optimal results. <h3>Reference</h3> [1] Nadkarni S, et al. Investigational analysis reveals a potential role for neutrophils in GCA disease progression. Circ. Res. 2014;114:242–48. <h3>Acknowledgements</h3> The authors would like to thank the Rotary club Zgornji Brnik, Slovenia, as well as Prof. Mauro Peretti and Dr. Suchita Nadkarni from WHRI, Queen Mary, University of London for their support. The research was conducted within the National Research Programme (#P3–0314), financially supported by the Slovenian Research Agency. <h3>Disclosure of Interest</h3> None declared