Background/Purpose: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are two closely related syndromes affecting older people. Proinflammatory cytokine IL-6 is found increased in both GCA/PMR patients and in the aged healthy population[1]. Pro-inflammatory monocytes, identified by CD16 and CD14 expression, increase with age and are potent producers of IL-6[2]. Importantly, monocyte-derived macrophages have been identified in the inflamed arteries of GCA and contribute to the immunopathology of GCA[3].  Yet, peripheral monocyte subsets are less well studied in GCA and PMR patients. In the current study, we assessed the distribution of different monocyte subsets in newly diagnosed GCA  and PMR patients before and after glucocorticoid (GC) treatment.

Methods: Peripheral blood samples of 16 newly-diagnosed GCA patients, 17 newly-diagnosed PMR patients and 16 age-matched, healthy controls (HCs) were studied. In a prospective, longitudinal study design, samples were obtained from 12 GCA and 10 PMR patients who were in remission after 12 weeks of treatment with GCs. Absolute numbers of total monocytes and classical(CD14^brightCD16^–), intermediate(CD14^brightCD16^dim) and non-classical(CD14^dimCD16^bright) monocytes were determined by truecount and flow cytometry. 

Results: Total numbers of circulating monocytes were increased in newly-diagnosed PMR patients but not in GCA patients when compared to age-matched HCs. Following 12 weeks of GC treatment, monocyte numbers normalized in PMR patients. When analysing absolute numbers of classical, intermediate and non-classical monocytes, we found the classical monocytes increased in PMR. No significant changes were noted in GCA. GC treatment in GCA tended to decrease numbers of non-classical monocytes (p=0.091).

When analysing relative changes in monocyte composition, the increase in classical monocytes in PMR was mirrored by a relative decrease of non-classical monocytes while proportions of intermediate type monocytes were unchanged. Interestingly, although we did not detect significant changes in absolute numbers, a similar decrease of non-classical monocytes was observed in newly diagnosed GCA patients. Moreover, GC treatment of GCA led to a further relative decrease of non-classical monocytes only.

Conclusion: We are the first to show that peripheral monocyte numbers are modulated during active PMR but not GCA. Treatment with GCs normalised monocyte numbers in PMR. Active disease in both PMR and GCA led to changes in monocyte composition showing decreases of non-classical monocytes. Different dynamics of monocyte subset distribution in PMR and GCA may help to unravel disease pathogenesis. Additional studies on different subsets of monocytes in GCA and PMR are ongoing.

References:

1. van der Geest K.S.M, et al. “Serum markers associated with disease activity in giant cell arteritis and polymyalgia rheumatica.” Rheumatology (2015)
2. Nyugen J., et al. “Impaired functions of peripheral blood monocyte subpopulations in aged humans.” Journal of clinical immunology 30.6 (2010): 806-813.
3. Rittner H.L., et al: Tissue-destructive macrophages in giant cell arteritis. Circulation research 1999, 84(9):1050-1058.

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/active-pmr-and-gca-is-associated-with-changes-in-monocyte-subset-composition/