Abstract
Early diagnosis and treatment of giant cell arteritis (GCA) is crucial for preventing ischemic complications. Multiple serological markers have been identified; however, there is a distinct lack of predicting markers for GCA relapse and complications. Our main objective was to identify serological parameters in a large cohort of treatment-naïve GCA patients, which could support clinicians in evaluating the course of the disease. Clinical data was gathered, along with analyte detection using Luminex technology, ELISA, and nephelometry, among others. Unsupervised hierarchical clustering and principal component analysis of analyte profiles were performed to determine delineation of GCA patients and healthy blood donors (HBDs). Highest, significantly elevated analytes in GCA patients were SAA (83-fold > HBDs median values), IL-23 (58-fold), and IL-6 (11-fold). Importantly, we show for the first time significantly changed levels of MARCO, alpha-fetoprotein, protein C, resistin, TNC, TNF RI, M-CSF, IL-18, and IL-31 in GCA versus HBDs. Changes in levels of SAA, CRP, haptoglobin, ESR, MMP-1 and MMP-2, and TNF-alpha were found associated with relapse and visual disturbances. aCL IgG was associated with limb artery involvement, even following adjustment for multiple testing. Principal component analysis revealed clear delineation between HBDs and GCA patients. Our study reveals biomarker clusters in a large cohort of patients with GCA and emphasizes the importance of using groups of serological biomarkers, such as acute phase proteins, MMPs, and cytokines (e.g. TNF-alpha) that could provide crucial insight into GCA complications and progression, leading to a more personalized disease management.
Highlights
Giant cell arteritis (GCA) is characterized by general symptoms, such as fatigue and weight loss, and ischemic symptoms, such as severe headaches, vision disturbances, and jaw claudication [1]
We focused on providing the most optimal serum analytes that would allow us to characterize treatment-naïve GCA patients and shed light on their different clinical manifestations
We show for the first time significantly changed levels of macrophage receptor with collagenous structure (MARCO), alpha-fetoprotein, protein C, resistin, tenascin C (TNC), TNF RI, M-CSF, IL-18, and IL-31 in GCA
Summary
Giant cell arteritis (GCA) is characterized by general symptoms, such as fatigue and weight loss, and ischemic symptoms, such as severe headaches, vision disturbances, and jaw claudication [1]. Cid et al reported that presence of a strong acute phase response defined a subgroup of patients with very low risk of developing visual loss and cranial ischemic complications in GCA [20]. A current comprehensive review on serological markers in GCA [21] highlights and confirms IL-6, as significantly and prevalently elevated in sera of GCA patients, and acute phase parameters (e.g., C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum amyloid A (SAA), haptoglobin and fibrinogen) as an added value for distinguishing subgroups of GCA patients with visual disturbances and predicting relapses. We set out to measure and analyze serological analytes in a large cohort of clinically wellcharacterized untreated GCA patients that could help clinicians evaluate the course of the disease, including relapse/ complications
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