Dermatologic and Ocular Diseases
Serum thymus and activation-regulated chemokine (TARC) and cutaneous T cell–attracting chemokine (CTACK) levels in allergic diseases: TARC and CTACK are disease-specific markers for atopic dermatitis

https://doi.org/10.1016/j.jaci.2003.12.007Get rights and content

Abstract

Background

Tissue infiltration of CD4+ T cells plays an important role in the pathogenesis of allergic diseases. T-cell trafficking is mediated by specific chemokines and their receptors.

Objective

The purpose of this study was to investigate the participation of the chemokines thymus and activation-regulated chemokine (TARC) and cutaneous T cell–attracting chemokine (CTACK) in a large population of patients with allergic diseases.

Methods

Serum TARC and CTACK levels were measured in 455 patients with allergic disease. Patients were characterized as having atopic dermatitis (AD), allergic asthma, allergic rhinitis, or combinations or as healthy control subjects. Serum TARC and CTACK levels were correlated with disease activity in patients with AD. Furthermore, in 7 patients with AD, serum TARC and CTACK levels were studied after the start of systemic cyclosporin A treatment. Finally, TARC and CTACK localization was checked by immunohistochemistry in lesional skin biopsy specimens of patients with AD.

Results

Both TARC and CTACK serum levels in patients with AD were significantly higher than those in healthy control subjects and patients with allergic respiratory disease. Furthermore, serum TARC and CTACK levels significantly correlated with disease activity in patients with AD. Serum TARC levels paralleled clinical improvement in patients treated with cyclosporin A. Immunoreactive TARC was found in infiltrating cells and endothelial cells of the dermis but not in epidermal cells.

Conclusions

The serum TARC level is an objective parameter for disease severity specific for AD. Furthermore, it is a promising tool for treatment monitoring.

Section snippets

Patients and samples

Sera from 455 human subjects were obtained (Table I). Patients with AD were diagnosed according to the criteria of Hanifin and Rajka.19 Patients with AR were diagnosed on the personal history of allergic symptoms and a positive nasal provocation, as described by Lebel et al.20 Patients with AA were selected on having a methacholine PC20 of ≤9.8 mg/mL or a reversibility of ≥9% after inhalation of salbutamol.

Severity of AD was evaluated by using the Leicester Sign Score (LSS; range, 0 to 108), in

Serum TARC and CTACK levels are specifically elevated in patients with AD

As shown in FIG 1, FIG 2, serum TARC and CTACK levels were increased in all 4 groups of patients with AD with statistical significance (P < .001) compared with both nonallergic subjects (HCs) and patients with allergic respiratory disease only (AR, AA, and AA + AR).

Serum TARC and CTACK levels correlate with disease activity in AD

Serum TARC and CTACK levels correlated with LSS severity scores (r = 0.56 and 0.52, respectively; P < .001) (Fig 3). No significant correlation was found between serum TARC levels and Lebel score in any of the patient groups with AD

Discussion

To evaluate a possible role for serum chemokine levels in atopic diseases, we determined serum TARC and CTACK levels in phenotypically well-defined groups of allergic patients. We conclude that serum TARC levels are specifically elevated in patients with AD irrespective of allergic respiratory comorbidity. Several recent reports have suggested that TARC might be important not only in allergic skin disease but also in allergic respiratory diseases (AA and AR).11, 13 The discrepancy between our

Acknowledgements

We thank the DUMAS group39 and Marja Oldhoff for collecting the patient serum samples. We also thank Inge de Vegt and Marloes Laaper for excellent technical support.

References (40)

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    Furthermore, the AD patients' plasma miR-191 levels were significantly correlated with their serum TARC levels (r = 0.60, P = 0.024), but not with their eosinophil counts (r = 0.21, P = 0.458), serum IgE levels (r = 0.18, P = 0.513), or serum LDH levels (r = 0.48, P = 0.071) (Fig. 3). These results indicate that plasma miR-24 and miR-191 levels are associated with the serum TARC level, which is considered to be a useful biomarker for monitoring AD severity [21,22]. We also examined the relationships between the AD patients' plasma miR-24 and miR-191 levels.

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