CCL17/thymus and activation–related chemokine in Churg‐Strauss syndrome

Abstract

Objective. Churg-Strauss syndrome (CSS) is a Th2-mediated systemic vasculitis characterized by eosinophilic infiltration, blood eosinophilia, and high IgE levels. CCL17/thymus and activation-regulated chemokine (TARC) is a chemokine responsible for the recruitment of Th2 cells. This study was undertaken to explore a possible role of CCL17/TARC in CSS.Methods. CCL17/TARC levels in serum from patients with active or inactive CSS, hypereosinophilic syndrome, systemic small-vessel vasculitis other than CSS, other types of eosinophilia, and healthy controls were determined by enzyme-linked immunosorbent assay. Biopsy samples of affected tissue from CSS patients were examined by immunohistochemical staining for Th2 infiltration and CCL17/TARC expression.Results. Serum CCL17/TARC levels were significantly elevated in CSS patients with active disease (mean ؎ SEM 1,122.0 ؎ 422.7 pg/ml) compared with controls (220.6 ؎ 27.9 pg/ml) and patients with inactive disease (388.9 ؎ 72.6 pg/ml) (P < 0.001 and P < 0.05, respectively). These levels correlated with the clinical disease course of CSS and with absolute eosinophil counts as well as IgE levels. Infiltrating Th2 cells in active CSS lesions were evidenced by CD294 staining. CCL17/TARC in the affected tissue of CSS patients was readily identified by immunohistochemical analysis. Elevated CCL17/TARC levels were also noted in patients with hypereosinophilic syndrome (794.5 ؎ 294.8 pg/ml) and other disorders associated with eosinophilia (1,096.0 ؎ 345.3 pg/ml) (both P < 0.005 versus controls).

Churg-Strauss Syndrome or Eosinophilic Granulomatosis with Polyangiitis

“…Although this biomarker needs diagnostic validation, it is likely to come into use in daily clinical practice. Recent studies have demonstrated elevated concentrations of proteins related to eosinophilia, particularly eotaxin-3, allowing to distinguish EGPA from other vasculitis or hyper-eosinophilia conditions [5]. Another marker of disease activity described in some studies is eosinophil cationic protein (ECP) [64].…”

“…Since anti-neutrophil cytoplasmic antibodies (ANCA) have been found in a proportion of patients, EGPA has subsequently been included in the spectrum of ANCA-associated vasculitis (AAV), along with GPA and microscopic polyangiitis (MPA) [4]. Several studies have elucidated the role of immune mechanisms, identifying genetic associations with HLA-DRB4 while recognizing new diagnostic and follow-up biomarkers (e.g., eotaxin-3) [5][6][7][8][9][10][11]. Finally, the treatment approach has improved through the use of immunosuppressive drugs and biological treatments.…”

Churg Strauss Syndrome: Clinical and Pathogenetic Approach to Therapy

“…Promising markers of the disease are those referring to activity and survival of eosinophils, like serum eosinophil cationic protein (Guilpain P et al, 2007), IL-5 (Tsukadaira A et al, 1999) or eotaxin-3 (CCL26), an eosinotactic chemokine mainly expressed on vascular endothelial cells and dermal fibroblasts (Polzer K et al, 2008). Recently, serum levels of TARC have been reported to be significantly elevated in CSS patients with active disease, and to correlate with the clinical course of the disease and with the absolute eosinophil counts, as well as with IgE levels (Dallos T et al, 2010). No confirmatory data are otherwise reported about the role of other eosinophil survival related molecules and interaction with the endothelium.…”

“…Given the expression profile of its receptors and the ability of CCL17/TARC to selectively induce migration of CD4+CD45RO+ T cells producing Th2 cytokines , it may be crucial for the specific recruitment and trafficking of Th2 cells, which are known to be activated in CSS. CCL17/TARC in the affected tissue of CSS patients is readily identified by immunohistochemical analysis, thus it may contribute to CSS pathogenesis by recruitment of Th2 cells into affected tissue (Dallos T et al, 2010).…”

Clinical management of the hypereosinophilic syndromes

“…Although this has not been investigated prospectively in this setting, evidence along this line has been produced for other diseases, namely Churg-Strauss syndrome and cutaneous T-cell lymphoma [79,80]. Measurement of serum TARC is reproducible and straightforward but is not performed in routine laboratories.…”