Blood Biomarkers for Monitoring and Prognosis of Large Vessel Vasculitides

Abstract

Purpose of Review Large vessel vasculitides (LVVs) are inflammatory conditions of the wall of large-sized arteries, mainly represented by giant cell arteritis (GCA) and Takayasu arteritis (TA). The inflammatory process within the vessel wall can lead to serious consequences such as development of aneurysms, strokes and blindness; therefore, early diagnosis and follow-up of LVV are fundamental. However, the arterial wall is poorly accessible and blood biomarkers are intended to help physicians not only in disease diagnosis but also in monitoring and defining the prognosis of these conditions, thus assisting therapeutic decisions and favouring personalised management. The field is the object of intense research as the identification of reliable biomarkers is likely to shed light on the mechanisms of disease progression and arterial remodelling. In this review, we will discuss the role of blood biomarkers in LVVs in the light of the latest evidence. Recent Findings In clinical practice, the most widely performed laboratory investigations are the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). However, these indices may be within normal limits during disease relapse and they are not reliable in patients receiving interleukin-6 (IL-6) receptor inhibitors. New biomarkers struggle to gain traction in clinical practice and no molecule with good accuracy has been identified to date. IL-6, a pro-inflammatory cytokine that drives CRP synthesis and increases the ESR, is one of the most promising biomarkers in the field. IL-6 analysis is increasingly performed, and serum levels are more sensitive than ESR for active GCA and might reflect persistent inflammation with high risk of relapse in patients on IL-6 receptor inhibitors. A future with biomarkers that reflect different disease features is an important aspiration. Accordingly, intense effort is being made to identify IL-6-independent inflammatory biomarkers, such as S100 proteins, pentraxin-3 and osteopontin. Moreover, metalloproteinases such as MMP2/9 and angiogenic modulators such as VEGF, YLK-40 and angiopoietins are being studied as markers of arterial remodelling. Lastly, biomarkers indicating organ damage may guide prognostic stratification as well as emergency therapeutic decisions: the most promising biomarkers so far identified are NT-proBNP, which reflects myocardial strain; pentraxin-3, which has been associated with recent optic nerve ischemia; and endothelin-1, which is associated with ischaemic complications. Summary Currently, the use of these molecules in clinical practice is limited because of their restricted availability, lack of sufficient studies supporting their validity and associated costs. Further evidence is required to better interpret their biological and clinical value.

Functionally Heterogenous Macrophage Subsets in the Pathogenesis of Giant Cell Arteritis: Novel Targets for Disease Monitoring and Treatment

“…As novel biomarker candidates, proteins released by macrophages important in the pathology of GCA may provide a source of biomarkers for diagnosis and tracking disease activity. Indeed, levels of macrophage products such as soluble CD163, YKL-40, Angiopoietin-2 (Angpt-2), IL-33, VEGF, MMP-9, calprotectin and osteopontin were found elevated in the serum of GCA patients compared to healthy donors [51,[104][105][106][107][108][109][110][111][112] (Figure 3). Several markers are altered in GCA compared to healthy controls.…”

“…Some studies reported markers to differentiate GCA patients from patients with isolated polymyalgia rheumatica (PMR). There is currently no macrophage markers to discriminate between GCA and infection (e.g., respiratory and urinary infection) [51,[104][105][106][107][108][109][110][111][112].…”

Application progress of multiple imaging modalities in Takayasu arteritis

“…Biomarkers can be used to diagnose or monitor disease activity for TA, which was given a minute description in related articles [87][88][89]. These biomarkers include tumor necrosis factor (TNF-α), vascular endothelial growth factor (VEGF), interleukins (ILs), pentraxin-3 (PTX-3), matrix metalloproteinases (MMPs), serum amyloid A (SAA), and chitinase-3-like protein 1 (YKL-40), and so on.…”

Using the co-expression network of T cell-activation-related genes to assess the disease activity in Takayasu’s arteritis patients

“…In addition, there are other potential blood biomarkers for monitoring the progress of TAK [ 4 ], such as pentraxin-3 [ 5 ], YKL-40 [ 6 ], MMP-9 [ 7 ], MMP-3 [ 8 ], leptin [ 9 ], and serum amyloid A [ 9 ]. However, the diagnostic efficacies of these biomarkers have not been clinically validated.…”