From Active to Non-active Giant Cell Arteritis: Longitudinal Monitoring of Patients on Glucocorticoid Therapy in Combination With Leflunomide

Abstract

In the present study, we longitudinally monitored leukocyte subsets, expression of neutrophil surface adhesion molecules (CD62L and CD11b) and serum analytes in therapy-naïve patients with active giant cell arteritis (GCA). We collected blood samples at the baseline, and at weeks 1, 4, 12, 24, and 48 of follow-up, and evaluated short- and long-term effects of glucocorticoids (GC) vs. GC and leflunomide. Our aim was to identify candidate biomarkers that could be used to monitor disease activity and predict an increased risk of a relapse. Following high doses of GC, the numbers of CD4+ T-lymphocytes and B-lymphocytes transiently increased and then subsided when GC dose tapering started at week 4. In contrast, the numbers of neutrophils significantly increased during the follow-up time of 12 weeks compared to pre-treatment time. Neutrophil CD62L rapidly diminished after initiation of GC therapy, however its expression remained low at week 48, only in patients under combinatorial therapy with leflunomide. Levels of acute phase reactant SAA and IL-6 decreased significantly after treatment with GC and leflunomide, while levels of IL-8, IL-18, and CHI3L1 did not change significantly during the follow-up period. CHI3L1 was associated with signs of transmural inflammation and vessel occlusion and might therefore serve as a marker of fully developed active GCA, and a promising therapeutic target. Patients with relapses had higher levels of IL-23 at presentation than patients without relapses (p = 0.021). Additionally, the levels of IL-23 were higher at the time of relapse compared to the last follow-up point before relapse. IL-23 might present a promising biomarker of uncontrolled and active disease and could give early indication of upcoming relapses.

New blood biomarkers and imaging for disease stratification and monitoring of giant cell arteritis

“…In that study, relapses were the main outcome, defined by the presence of new or increasing clinical symptoms requiring treatment intensification. 19 …”

“…In that study, relapses were the main outcome, defined by the presence of new or increasing clinical symptoms requiring treatment intensification. 19 Other potential monitoring biomarkers include the B cell activating factor (BAFF) 20 and serum osteopontin. 21 BAFF is a key regulator of B cell responses, produced mainly by stromal cells but also by monocytes following exposure to proinflammatory cytokines such as interferon-gamma.…”

Giant Cell Arteritis: Advances in Understanding Pathogenesis and Implications for Clinical Practice

“…Also of interest is the increase in the level of IL-23, found elevated in the serum of patients with GCA [149]. Since this cytokine secreted by dendritic cells is necessary for the differentiation and survival of Th17 cells, which exert their pathogenic role through IL-17 synthesis, this suggested the possible use of biologics targeting these interleukins in therapy.…”