THU0043 EXPRESSION OF B CELL CHEMOKINE-CHEMOKINE RECEPTOR PATHWAYS IS ALTERED IN GIANT CELL ARTERITIS
Authors: J. Graver, A. Boots, W. Abdulahad, J. Bijzet, D. Wolbers, E. Brouwer, M. Sandovici
Journal: Annals of the Rheumatic Diseases (2020)

Background: The presence of organised B cells in both cranial-giant cell arteritis (C-GCA) (temporal artery) and large vessel (LV)-GCA (aorta) has previously been documented. The number and the extent of organisation of B cells in tertiary lymphoid organs (TLO) was more prominent in the aorta than in the temporal artery, suggesting possible differences in B cell phenotype, kinetics and tropism between C-GCA and LV-GCA. Objectives: We sought to analyse B cell differentiation subsets in both C-GCA and LV-GCA and to investigate differences in the expression of chemokine pathways involved in B cell migration and TLO organisation. Methods: Blood was collected from C-GCA (n=11) and LV-GCA (n=22) patients at baseline, before start of glucocorticoid treatment, and after 3 months of treatment. The LV-GCA groups consisted of 11 patients with isolated LV-GCA and 11 patients with overlap LV/C-GCA. Also, age- and sex- matched healthy controls (HC, n=24) were included. The following chemokines were measured with Luminex in the sera of patients and HC: BAFF, CCL19, CCL21, CXCL9, CXCL10, CXCL11, CXCL12, and CXCL13. Thawed PBMC of 7 C-GCA, 10 LV-GCA and 24 HC were stained with antibodies against CD19, CD27, IgD, IgM, CD38, CXCR3, CXCR4, CXCR5, and CCR7 to allow identification of B cell differentiation subsets and their chemokine receptor expression. Results: We found a lower absolute number of CXCR3+ memory and double negative (late stage) B cells in GCA patients when compared to healthy controls. Also, the absolute number of CXCR5+ memory B cells was lower in patients than in controls. Chemokine receptor expression on circulating B cells did not significantly differ between C-GCA and LV-GCA at baseline. After 3 months of treatment, frequencies and absolute numbers of both CXCR3+ and CXCR5+ memory B cells increased. In sera of all GCA patients, CXCL9 (which is a chemokine involved in migration of B cells to sites of inflammation) and CXCL13 (which is involved in local organization of B cells) were significantly increased. BAFF and CCL21 were increased only in LV-GCA when compared to HC. Serum chemokine levels did not differ between C-GCA and LV-GCA patients. An inverse correlation was observed between B cell counts and CXCL9 as well as CXCL13 in LV-GCA, only. After 3 months of treatment, CXCL9 levels remained elevated whereas CXCL13 increased even further. Conclusion: At diagnosis, CXCL9 and CXCL13 were significantly increased in all GCA patients as compared to HC. Elevated CXCL9 levels inversely correlated with B cells numbers in LV-GCA, only, which may suggest that B cells preferentially migrate to the inflamed aorta via a mechanism involving CXCL9. In addition, CXCL13 may be linked to local TLO organization in LV-GCA. Currently, we are studying the local expression of chemokines and chemokine receptors at the site of inflammation in both C- and LV-GCA. Disclosure of Interests: Jacoba Graver: None declared, Annemieke Boots Consultant of: Grünenthal Gmbh until 2017, Wayel Abdulahad: None declared, Johan Bijzet: None declared, Daphne Wolbers: 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), Maria Sandovici: None declared