Abstract

Background: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are inflammatory diseases requiring long-term treatment with glucocorticoids. Currently, only limited data on dynamics of peripheral leukocytes and leukocyte subset composition before, during and after treatment is available. Objectives: To gain insight into the dynamics of leukocytes during the entire disease course and to determine whether patients in treatment-free remission resemble healthy controls. Methods: Newly-diagnosed, treatment-naive GCA (N=42) and PMR (N=31) patients were prospectively followed for up to 7 years. Absolute numbers of leukocyte subpopulation, both myeloid (neutrophils, monocytes) and lymphoid (CD4 and CD8 T-cells, B-cells and NK-cells) were measured at fixed time points. Laboratory inflammation markers (CRP, ESR, platelets and haemoglobin) were assessed as well. Values were compared with age-matched healthy controls (N=51) and infection controls (N=13). A stable treatment-free remission group for at least 6 months was defined. Results: Neutrophil and monocyte numbers were higher in baseline GCA and PMR patients compared to healthy controls, whilst NK-cell numbers were reduced. In baseline GCA patients, CRP correlated positively with monocyte numbers. In baseline PMR patients, B-cell numbers were lowered and B-cell and NK-cell numbers correlated negatively with CRP. During glucocorticoid treatment, fluctuations in numbers of all leukocyte subsets were observed but neutrophil and monocyte numbers remained elevated and NK-cells numbers remained lowered during the entire treatment period (fig. 1). CRP and ESR were reduced by GC treatment and only moderately elevated during relapses. GCA patients in treatment-free remission still had elevated neutrophil and monocyte numbers. In addition, ESR and platelet numbers, were elevated whilst haemoglobin was lowered. PMR patients in treatment-free remission still had elevated monocytes while NK-cell and CD8+ T-cell numbers were decreased. Inflammatory markers and haemoglobin was normal. Conclusion: In baseline GCA and PMR patients a shift towards the myeloid lineage is observed. This myeloid bias persisted in spite of GC treatment and also in treatment-free remission, suggesting a long-term effect of inflammation (an inflammatory imprint) on the peripheral blood compartment. Only GCA patients showed persistently elevated inflammatory markers; whether this reflects ongoing subclinical disease remains to be investigated. Disclosure of Interests: Jacoba Graver: None declared, Yannick van Sleen: None declared, Wayel Abdulahad: None declared, Kornelis van der Geest: None declared, Annemieke Boots Grant/research support from: grant from MSD in 2010-2015, Consultant for: I was a consultant for Grunenthal Germany 2016-2017, Employee of: I was an employee of Organon, Shering-Plough and MSD from 1991-2011, Maria Sandovici: None declared, Elisabeth Brouwer Speakers bureau: Dr. Brouwer as an employee of the UMCG received speaker fees and consulting fees from Roche which were paid to the UMCG

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