AB0046 NO EVIDENCE FOR DISTURBED TH1 AND TH17 FREQUENCIES IN GCA AND PMR PATIENTS - A STUDY IN THE GRONINGEN GPS COHORT
Authors: Y. Van Sleen, E. Brouwer, M. G. Huitema, W. Abdulahad, M. Sandovici, A. Boots, K. Van der Geest
Journal: Annals of the Rheumatic Diseases (2020)

Background: Giant cell arteritis (GCA) is an aging-associated inflammatory disease of the large-sized arteries. GCA clinically and pathogenically overlaps with polymyalgia rheumatica (PMR), which affects the shoulders and hips. In the inflamed tissues, infiltrated CD4+ T-cells display a disturbed Th cell distribution, that may contribute to the development of the diseases. GCA arteries contain pro-inflammatory T-helper 1 (Th1) and Th17 cells, but almost no Th2 cells or regulatory T-cells. In addition to CD4+ T-cells, macrophages are dominant in GCA and PMR tissue infiltrates. We previously found an altered distribution of monocyte subsets, the precursors of macrophages, in the blood of GCA and PMR patients. Others reported changes in the distribution of Th cells in the blood of treatment-naive GCA and PMR patients as well. Objectives: We sought to replicate previous studies showing a disturbed Th cell distribution in the blood of GCA and PMR patients. Next, we aimed to link the disturbed Th cell distribution to the altered monocyte subset counts. Methods: To assess the capacity of circulating T cells to produce lineage cytokines, PBMCs were cultured for 4 hours in the presence of 50 n g/mL PMA, 1.6 μg/mL calcium ionophore and 10μg/mL BFA. Cells were then intracellularly stained for IFNγ (Th1 cells), IL-17 (Th17 cells) and IL-4 (Th2) by flow cytometry. In addition, monocyte subset counts were determined, based on CD14 and CD16 expression. To obtain absolute counts, proportions determined by flow cytometry were corrected by the total CD4+ T-cell and monocyte counts. Th1, Th17 and monocyte subsets were determined in 21 GCA patients, 19 PMR patients and 19 healthy controls (HC). Th2 cells were determined in 10 GCA patients, 10 PMR patients and 10 HC. All GCA and PMR patients were newly-diagnosed and treatment-naive. HC were age- and sex-matched and without any immunomodulatory medication. Results: Both absolute counts and percentages of peripheral Th1 cells, Th17 cells and Th2 cells did not differ between GCA/PMR patients and HC. The monocytosis in GCA and PMR was mainly attributed to an expansion of the classical monocyte subset. Counts of monocyte subsets were not strongly correlated with counts of either Th1 or Th17 cell counts. In GCA patients, the ESR correlated positively with counts of intermediate monocytes (R= 0.63), but this was not observed in PMR patients. Conclusion: Compared to most previous work, we report similar circulating Th1 and Th17 cell counts in HC, but lower counts in treatment-naive GCA patients then previously reported (Table 1). Furthermore, numbers of Th1 and Th17 cells in peripheral blood showed no relationship with monocyte subsets. As our protocol for defining Th1 and Th17 cells appears to be similar to the other studies, we propose differences in patient selection. Alternatively, Th1 and Th17 skewing should be studied at the site of inflammation, since Th1 and Th17 skewing cytokines are all highly expressed by macrophages at the inflammatory site. This study shows the importance of replicating previous research, as key concepts of disease pathology are derived from data on disturbed Th cell distribution. Table 1. Observed median percentages of circulating Th1 and Th17 cells in GCA patients and age-matched HC. Shown are outcomes from several previous studies as well as the present study. Deng et al, Terrier et al and Saadoun et al found elevated Th1 cell percentages in GCA, whereas Samson et al found them lower. All four previous studies showed elevated Th17 percentages in GCA. Th1% Th17% Reference GCA HC GCA HC Deng et al., Circulation , 2010 20 12 2.2 0.4 Terrier et al., Arthritis Rheumatol , 2012 22 12 2.5 0.5 Saadoun et al., Arthritis Rheumatol , 2015 22 17 2.5 0.6 Samson et al., Arthritis Rheumatol , 2012 10 14 0.7 0.3 This study 11 12 0.6 0.5 Disclosure of Interests: Yannick van Sleen: None declared, Elisabeth Brouwer Consultant of: Roche (consultancy fee 2017 and 2018 paid to the UMCG), Speakers bureau: Roche (2017 and 2018 paid to the UMCG), Minke G. Huitema: None declared, Wayel Abdulahad: None declared, Maria Sandovici: None declared, Annemieke Boots Consultant of: Grünenthal Gmbh until 2017, Kornelis van der Geest Speakers bureau: Roche (2019)