Dermatologic and Ocular Diseases
Presence of high contents of thymus and activation-regulated chemokine in platelets and elevated plasma levels of thymus and activation-regulated chemokine and macrophage-derived chemokine in patients with atopic dermatitis,☆☆

https://doi.org/10.1067/mai.2002.126079Get rights and content

Abstract

Background: TH2 cells and eosinophils selectively express CC chemokine receptor 4 and CCR3, respectively, and their chemokine ligands are likely to play important roles in the pathogenesis of atopic dermatitis (AD). Objective: The purpose of this study was to demonstrate the presence of thymus and activation-regulated chemokine (TARC) in platelets and its release during clotting and to evaluate the circulating levels of TARC, macrophage-derived chemokine (MDC), and eotaxin in control subjects and patients with AD. Methods: We compared plasma and serum contents of TARC, MDC, and eotaxin. We measured TARC contents in platelet lysates. We analyzed the correlation of plasma levels of TARC, MDC, and eotaxin with various clinicolaboratory parameters in patients with AD. Results: Serum contents of TARC rapidly increased during clotting, whereas those of MDC and eotaxin increased only slightly. We demonstrated that platelets contained TARC, and its levels were dramatically elevated in patients with AD. Platelets also released TARC on stimulation with thrombin. We therefore evaluated circulating levels of these chemokines in control subjects and patients with AD by using plasma samples. Plasma TARC levels were significantly increased in patients with AD (P < .0001) and showed significant correlations with severity scoring of atopic dermatitis (SCORAD) index (r = 0.665, P < .00001), serum lactate dehydrogenese levels (r = 0.696, P = .00001), eosinophil counts (r = 0.381, P = .007), and platelet counts (r = 0.562, P < .0001). Similarly, plasma MDC levels were significantly increased in patients with AD (P < .0001) and showed significant correlations with SCORAD index (r = 0.727, P < .0001), serum lactate dehydrogenese levels (r = 0.861, P < .0001), eosinophil counts (r = 0.505, P = .005), and platelet counts (r = 0.370, P = .01). On treatment, plasma TARC and MDC levels were dramatically decreased in accordance with improved SCORAD scores (P = .0012 and P = .0007, respectively). On the other hand, plasma eotaxin levels did not show any significant increase or correlation with any of the clinical parameters in patients with AD. Conclusion: Platelets from patients with AD contain high levels of TARC. Thus platelets might play an important role in AD pathogenesis by releasing TH2-attracting TARC on activation. Furthermore, circulating levels of TARC and MDC, but not those of eotaxin, correlate well with the disease activity of AD. (J Allergy Clin Immunol 2002;110:139-46.)

Section snippets

Subjects and samples

A total of 29 patients with AD (22 children <16 years of age and 7 adults ≥16 years) and 29 healthy age-matched donors (19 children <16 years of age and 10 adults ≥16 years) were examined. Mean age ± SD was 8.0 ± 5.0 in children with AD, 9.9 ± 3.8 in control children, 24.6 ± 4.7 in adults with AD, and 27.8 ± 3.8 in control adults. The healthy control subjects had no history of allergic diseases, and their serum IgE levels were less than 160 IU/mL, with no detectable specific IgE antibodies to

Rapid increases in serum tarc/ccl17 levels during blood clotting

We simultaneously collected plasma and serum samples from control subjects and patients with AD and determined the contents of TARC/CCL17, MDC/CCL22, and eotaxin/CCL11. As shown in Fig 1, TARC contents were dramatically increased in the serum samples.

. Comparison between plasma and serum for contents of TARC, MDC, and eotaxin. Plasma and serum samples were simultaneously obtained from control subjects (n = 21) and patients with AD (n = 14). Amounts of TARC, MDC, and eotaxin were measured with

Discussion

Platelets play an important role not only in blood coagulation but also in inflammation.19, 20 Involvement of platelets in the pathogenesis of allergen-induced asthma has been reported.21, 22 Selective depletion of circulating platelets was shown to reduce the late-phase response, eosinophil infiltration, and bronchial hyperresponsiveness in animal models of asthma.23, 24 Platelets are also known to release various chemokines.25, 26, 27 Release of RANTES from platelets on cross-linking of the

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    Citation Excerpt :

    Direct correlations of TARC levels in the blood with AD severity have been found in both children and adults4-6,13,16 and confirmed by a meta-analysis.3 In response to therapy, a decrease in TARC levels has been reported for topical corticosteroids,5 ciclosporin,6 mycophenolate sodium,8 and dupilumab.11,14 Application of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach revealed that TARC levels in blood show a high level of evidence as a biomarker for AD correlating with its severity.2

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Supported by grants from the Ministry of Health, Labor and Welfare, and from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

☆☆

Reprint requests: Takao Fujisawa, MD, Department of Pediatrics and Allergy, National Mie Hospital, 357 Osato-Kubota, Tsu, Mie 514-0125, Japan; Osamu Yoshie, MD, Department of Microbiology, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama 589-8511, Japan.

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