Serum Levels Of Thymus And Activation-regulated Chemokine Research Articles

Effects of Dupilumab on Itch-Related Events in Atopic Dermatitis: Implications for Assessing Treatment Efficacy in Clinical Practice.

Dupilumab attenuates itch and skin inflammation in patients with atopic dermatitis (AD). However, itch-related events that are improved by dupilumab remain unclear. Therefore, the present study investigated changes in clinical scores, serum biomarkers, and the number of intraepidermal nerve fibers (IENFs) using skin biopsies and blood samples from 12 patients with moderate to severe AD before and after treatment with dupilumab. Clinical manifestations were assessed using eczema area and severity index (EASI) and visual analogue scale (VAS) scores at baseline and after 8 and 16 weeks of treatment. Serum levels of total immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), interleukin (IL)-4, IL-13, IL-22, and IL-31 were examined by electrochemiluminescence, chemiluminescent enzyme immunoassays, ProQuantum immunoassays, and enzyme-linked immunosorbent assays (ELISA) at baseline and after 8 and 16 weeks of treatment. In skin biopsies from AD patients at baseline and after 16 weeks of treatment, IENFs were examined immunohistochemically with the anti-protein gene product (PGP) 9.5 antibody. The dupilumab treatment significantly improved EASI and VAS scores and decreased serum levels of TARC, IgE, and IL-22, whereas those of IL-13 and IL-31, and the number of IENFs remained unchanged and those of IL-4 increased. VAS scores were positively correlated with serum TARC, IL-22, and IgE levels and the degree of epidermal thickening. Serum IL-31 levels were positively correlated with the number of IENFs. These results suggest that serum TARC, IL-22, and IgE levels and epidermal thickness are itch-related events associated with dupilumab treatment and that serum IL-31 levels may reflect the degree of IENF density in AD patients. Therefore, dynamic changes may be used to assess the efficacy of dupilumab treatment to treat itching and inflammation in patients with AD.

Real‐world effectiveness and safety of dupilumab in patients with moderate and severe atopic dermatitis: 2‐year experience

AbstractObjectiveDupilumab has been deemed highly effective for atopic dermatitis (AD). However, there have been no reports performing a combination analysis with hematological data and improvement rates pertaining to the continued use of dupilumab for up to 2 years in real world. In this study, we evaluated the effectiveness and safety of using dupilumab for up to 2 years in 9 patients with AD at our hospital.MethodsThirty‐six patients with moderate‐to‐severe AD treated by dupilumab, and 9 of them treated for 2 years. Changes in the severity scoring, pruritus numerical rating scale (NRS), patient‐oriented eczema measure (POEM), serum levels of immunoglobulin E (IgE), thymus and activation‐regulated chemokine (TARC), eosinophils, and lactate dehydrogenase (LDH) at Week 0, 2, 4, 16, 48, 72, and 96 of those patients were investigated, and we studied features of the patients who had any adverse events (AEs).ResultsInvestigator’s global assessment (IGA), eczema area and severity index (EASI), body surface area (BSA), NRS, POEM, and serum levels of LDH were significantly decreased from Week 4 onwards to Week 96 compared with baseline condition. Serum levels of TARC and LDH were significantly decreased from Week 4 onwards to Week 96. Regarding 9 patients who were treated with dupilumab for up to 2 years, serum levels of TARC and eosinophils decreased without statistical significance. The serum levels of IgE significantly decreased at Week 72, 96 compared with the baseline. Regarding as AEs, ocular symptoms were the most frequently observed (15/36, 41.2%), and there were no cases of discontinuation due to AEs.ConclusionsTreatment with dupilumab was well tolerated and showed improvements in AD for at least 2 years.

Serum thymus and activation-regulated chemokine (TARC) levels correlate with atopic dermatitis disease severity in patients < 6 months.

Background: Atopic dermatitis (AD) may develop by 6 months of age, and its severity assessment is essential for appropriate treatments. Scoring Atopic Dermatitis (SCORAD) is suggested to evaluate the severity of AD but is cumbersome for routine clinical use. The serum thymus and activation-regulated chemokine (TARC) is used as a marker of AD severity. However, the normal range of the TARC levels varies by age, and its usefulness for the evaluation of AD severity has not been established in patients ages < 6 months. Here, we evaluated the correlation between serum TARC levels and SCORAD scores in early infancy and sought the optimal cutoff level to indicate AD severity. Methods: The subjects were 35 patients with AD (16 girls and 19 boys; 3-5 months of age) who visited our clinic between April 2015 and March 2017. All the patients were physically examined by a board-certified allergist. The AD severity was determined by using the SCORAD, together with serum levels of TARC, total immunoglobulin E (IgE), lactate dehydrogenase, and peripheral eosinophil counts. Receiver operating characteristic curve analysis was performed to determine the cutoff levels of serum TARC to indicate AD severity. Results: Significant correlations were observed between SCORAD scores and the serum TARC levels, peripheral eosinophil counts, and serum IgE levels (r = 0.640, r = 0.723, r = 0.533, respectively). The optimal cutoff levels of serum TARC to indicate mild and severe AD were <3523 pg/mL (area under the curve [AUC] = 0.856) and >6192 pg/mL (AUC = 0.833), respectively. Conclusion: Although this study had limitations, we suggest that serum TARC is useful as a marker of AD severity in patients <6 months of age.

14402 Serum levels of thymus and activation-regulated chemokine in patients with psoriasis: Higher in patients with generalized pustular psoriasis

Thymus and activation-regulated chemokine (TARC) is designated a TH2 type chemokine. Serum TARC levels sharply reflect the disease activity of atopic dermatitis. The previous studies reported that serum TARC levels in patients with psoriasis vulgaris (PsV) were comparable with those in healthy controls, however, we sometimes encounter psoriasis patients with high serum levels of TARC. The association of clinical severity of psoriasis with serum TARC levels has not been investigated yet. Furthermore, to date, serum TARC levels in patients with psoriatic arthritis (PsA) or generalized pustular psoriasis (GPP) have never been reported. Thereby, we investigated the association of serum TARC levels with psoriasis by types of psoriasis, and examined correlations of serum TARC levels with clinical severity scores and other results of blood tests. Psoriasis patients visiting our hospital from April 2013 to April 2018 were included in this study. All data were collected retrospectively from the patient charts. Data on 75 patients (51 men and 24 women; PsV 30 patients, PsA 29 patients, GPP 16 patients) were analyzed. The serum TARC levels in patients with GPP were significantly higher than those in PsV and those in PsA. There was significantly positive correlation between serum TARC levels and PASI scores. In conclusion, our study revealed that serum TARC levels were high in patients with GPP. Furthermore, serum TARC levels can potentially be one of biomarkers reflecting the severity or systemic inflammation caused by psoriasis in patients with psoriasis, not so much as in patients with atopic dermatitis.

Thymus and activation-regulated chemokine (TARC/CCL17) predicts decline of pulmonary function in patients with chronic obstructive pulmonary disease

BackgroundThe deterioration of pulmonary function, such as FEV1-decline, is strongly associated with poor prognosis in patients with chronic obstructive pulmonary disease (COPD). However, few investigations shed light on useful biomarkers for predicting the decline of pulmonary function. We evaluated whether thymus and activation-regulated chemokine (TARC), a Th2 inflammation marker, could predict rapid FEV1-decline in COPD patients. MethodsWe recruited 161 patients with stable COPD and performed pulmonary function test once every six months. At the time of registration, blood tests, including serum levels of TARC were performed. We assessed the correlation between changes in parameters of pulmonary function tests and serum levels of TARC. The rapid-decline in pulmonary function was determined using 25th percentile of change in FEV1 or FEV1 percent predicted (%FEV1) per year. ResultsIn the FEV1-rapid-decline group, the frequency of exacerbations, the degree of emphysema, and serum levels of TARC was higher than in the non-rapid-decline group. When using %FEV1 as a classifier instead of FEV1, age, the frequency of exacerbations, the degree of emphysema and serum levels of TARC in the rapid-decline group was significantly greater than those in the non-rapid-decline group. In univariate logistic regression analysis, TARC was the significant predictive factor for rapid-decline group. In multivariate analysis adjusted for emphysema, serum levels of TARC are independently significant predicting factors for the rapid-decline group. ConclusionsTARC is an independent predictive biomarker for the rapid-decline in FEV1. Measuring serum TARC levels may help the management of COPD patients by predicting the risk of FEV1 decline.

Diagnostic value of thymus and activation-regulated chemokine and of periostin in eosinophilic asthma: A prospective study.

Serum thymus and activation-regulated chemokine (TARC) and periostin are reliable biomarkers in eosinophilicasthma. This study was carried out to determine the use of periostin and TARC as biomarkers in asthma and to comparethe superiority of one over the other, especially in asthma with an eosinophilic phenotype. The study was conducted with 87 patients with asthma and 42 healthy control subjects. Patients with asthma were also divided into eosinophilic and non-eosinophilic phenotypes. A pulmonary function test was performed in all the participants,and serum and induced sputum TARC, periostin concentrations, eosinophils, and total immunoglobulin E valueswere examined. TARC and periostin levels were significantly higher in the asthma group than in the control group (p < 0.001). The serum TARC level in the eosinophilic group was significantly higher than in the non-eosinophilic and control groups(p < 0.001). The induced sputum TARC level was significantly higher in the non-eosinophilic group than in the control group(p < 0.001). The TARC and periostin levels of the patients were evaluated by using receiver operator characteristic analysis.The cutoff value for TARC was determined to be 1415.39 ng/L; likewise, the cutoff value for periostin was 107.60 ng/L. Thepresent study detected that serum levels of TARC correlated to serum levels of periostin (r = 0.54; p = 0.032). Furthermore,when evaluating correlations between serum and sputum levels, there was a correlation detected between TARC and periostinin serum, whereas this correlation was stronger in sputum: r = 0.66, p = 0.020; and r = 0.62, p = 0.028, respectively. Serum and sputum TARC and periostin may contribute for monitoring the improvement of patients, particularly those with asthma. Furthermore, TARC was a more reliable biomarker than periostin for patients with eosinophilic asthma.

Conjunctivitis in patients with atopic dermatitis treated with dupilumab is associated with higher baseline serum levels of immunoglobulin E and thymus and activation-regulated chemokine but not clinical severity in a real-world setting

To the Editor: Conjunctivitis has been observed as an adverse event in patients with atopic dermatitis (AD) receiving dupilumab. Its incidence rate ranges from 8.6% to 21.44% in clinical trials,1Akinlade B. Guttman-Yassky E. de Bruin-Weller M. et al.Conjunctivitis in dupilumab clinical trials.Br J Dermatol. 2019; 181: 459-473Crossref PubMed Scopus (178) Google Scholar whereas real-world data have shown an even higher prevalence.2Uchida H. Kamata M. Mizukawa I. et al.Real-world effectiveness and safety of dupilumab for the treatment of atopic dermatitis in Japanese patients: a single-centre retrospective study.Br J Dermatol. 2019; 181: 1083-1085Crossref PubMed Scopus (25) Google Scholar We analyzed our data to explore practical predictors of later development of conjunctivitis in patients with AD initiating dupilumab in a real-world setting. The study included adult patients with AD who had been treated with dupilumab in our hospital for more than 3 months as of October 1, 2019. Other inclusion criteria were the same as those described in our previous report.2Uchida H. Kamata M. Mizukawa I. et al.Real-world effectiveness and safety of dupilumab for the treatment of atopic dermatitis in Japanese patients: a single-centre retrospective study.Br J Dermatol. 2019; 181: 1083-1085Crossref PubMed Scopus (25) Google Scholar Baseline clinical severity, patents’ history of conjunctivitis, and results from laboratory blood tests were compared between patients who developed conjunctivitis and those who did not. Data on 57 Japanese adult patients (49 men, 8 women) with AD were analyzed. The mean ± standard deviation age at starting dupilumab was 38.1 ± 11.8 years. Conjunctivitis was observed in 22.8% (13 of 57) of patients after starting dupilumab. The mean time to develop conjunctivitis after beginning dupilumab was 5.3 ± 3.9 weeks. Conjunctivitis developed at a higher frequency after starting dupilumab in patients who had a history of conjunctivitis at baseline than in those who did not. Patients in whom conjunctivitis occurred after starting dupilumab had significantly higher serum levels of thymus and activation-regulated chemokine (TARC) and immunoglobulin E (IgE) at baseline than those who did not (Fig 1). The cutoff values at baseline were 3342 pg/mL (sensitivity, 69.23%; specificity, 79.55%) for TARC and 11,200 IU/mL (sensitivity, 76.92%; specificity, 69.77%) for IgE, with moderate accuracy. No significant differences were observed between them in clinical severity, including Investigator's Global Assessment, affected body surface area, the Eczema Area and Severity Index, and results of other laboratory blood tests. Clinical trials have demonstrated that baseline disease-related factors, including AD severity, prior conjunctivitis history, and certain biomarkers (TARC, IgE, eosinophils), are associated with an increased incidence of conjunctivitis.1Akinlade B. Guttman-Yassky E. de Bruin-Weller M. et al.Conjunctivitis in dupilumab clinical trials.Br J Dermatol. 2019; 181: 459-473Crossref PubMed Scopus (178) Google Scholar It is reasonable, because levels of certain biomarkers, such as TARC, IgE, and eosinophils, increase with AD severity.3Beck L.A. Thaci D. Hamilton J.D. et al.Dupilumab treatment in adults with moderate-to-severe atopic dermatitis.N Engl J Med. 2014; 371: 130-139Crossref PubMed Scopus (879) Google Scholar, 4Hamilton J.D. Suarez-Farinas M. Dhingra N. et al.Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis.J Allergy Clin Immunol. 2014; 134: 1293-1300Abstract Full Text Full Text PDF PubMed Scopus (297) Google Scholar, 5Guttman-Yassky E. Bissonnette R. Ungar B. et al.Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis.J Allergy Clin Immunol. 2019; 143: 155-172Abstract Full Text Full Text PDF PubMed Scopus (244) Google Scholar However, our real-world data revealed that only baseline serum TARC and IgE levels were significantly higher in patients who developed conjunctivitis and that a history of conjunctivitis and eosinophils showed its tendency, whereas baseline clinical severity did not demonstrate any association with incidence of conjunctivitis. Even in data from clinical trials, the difference in the incidence of conjunctivitis between patients with AD with a baseline score of 3 on the 5-point Investigator's Global Assessment scale and those with a baseline of 4 was quite small in CHRONOS (NCT02260986) (0.06 vs 0.09 per 100 patient-years) and in CAFÉ (NCT02755649) (0.22 vs 0.23).1Akinlade B. Guttman-Yassky E. de Bruin-Weller M. et al.Conjunctivitis in dupilumab clinical trials.Br J Dermatol. 2019; 181: 459-473Crossref PubMed Scopus (178) Google Scholar Distinguishing the subtle differences in disease severity of AD among patients with moderate to severe AD (not including mild AD) is difficult for physicians. Our study underscores that among those parameters, serum levels of TARC and IgE could reflect subtle differences in predisposition for conjunctivitis more accurately than the disease severity of AD evaluated by physicians, especially among patients with moderate to severe AD, indicating that these objective parameters are useful as practical predictors of later development of conjunctivitis.

Serum levels of thymus and activation-regulated chemokine can be used in the clinical evaluation of atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by the predominant infiltration of Th2-type cells in lesional skin. Thymus and activation-regulated chemokine (TARC) is overproduced in AD patients, and its serum levels are significantly higher in individuals with AD than in those with other inflammatory skin diseases. The purpose of this study was to examine whether serum levels of TARC can assess the severity of AD and be used in the clinical evaluation of AD. A total of 73 AD patients, 11 patients with generalized atopic eczema (AE), and 30 healthy control subjects were enrolled. SCORAD (SCORing of Atopic Dermatitis) indices were calculated according to skin symptom scores. The Th2 chemokines TARC kit was then used to obtain serum TARC values in each group. Finally, statistical analysis was used to identify any correlations between serum TARC level and SCORAD index in AD and AE patients. Mean serum TARC values were 159.95 in healthy controls, 146.46 in the mild AD group, 202.71 in the moderate AD group, 1216.61 in the severe AD group and 1554.50 in the severe AE group. The serum TARC level was significantly correlated with SCORAD score in AD patients (P < 0.01). However, there was no significant correlation between SCORAD score and TARC in AE patients (P = 0.610). The serum TARC level can be used to assess the severity of AD and as a reference index for the fast clinical evaluation of AD.

Effect of camel milk on thymus and activation-regulated chemokine in autistic children: double-blind study

This study aimed to investigate the role of the effectiveness of camel milk (CM) (raw and boiled) on thymus and activation-regulated chemokine (TARC) serum levels and childhood autism rating scale (CARS) score in subjects with autism and compared to placebo group (cow milk). Forty-five subjects diagnosed with autism were randomly assigned to receive boiled CM for group I (n = 15), raw CM for group II (n = 15), and placebo for group III (n = 15) for 2 wk. Measures included changes in professionally completed CARS score and blood samples for TARC serum level were taken before and after milk consumption of 500 ml per day in children's regular daily diet. The serum levels of TARC decreased significantly (P = 0.004) in boiled CM and in raw CM group (P = 0.01) too, but no effect was observed (P = 0.68) in placebo group. Furthermore, significant improvements were observed in CARS score (P = 0.04) in raw CM group only. There were no significant relationships between the serum of TARC level and the CARS score, age, or gender for any group. CM administered for 2 wk significantly improved clinical measurements of autism severity and decreased serum level of TARC in autistic children, but subsequent studies are recommended.

The effects of narrow-band ultraviolet B on the expression of the CC subfamily of chemokines and its efficacy in treating patients with atopic dermatitis

Objective To observe the clinical efficacy of narrow-band ultraviolet B (NB-UVB) in the treatment of the patients with atopic dermatitis (AD) and the effects of NB-UVB on the expression of the CC subfamily of chemokines in AD patients. Methods Fifty-five AD patients were treated with NB-UVB with a starting dose of 50％ of the minimal erythma dose.ELISA was used to measure the serum levels of thymus and activation-regulated chemokine ( TARC),cutaneous T cell-attracting chemokine ( CTACK),macrophage-derived chemokine (MDC) and eotaxin in all of the patients before and after treatment,and the clinical efficacy was evaluated.The scores on an atopic dermatitis index (SCORAD) and a visual analogue scale were used for the clinical evaluation.Thirty healthy persons were recruited and served as normal controls. Results The serum levels of TARC,CTACK and MDC were significantly higher in patients with AD than in the normal controls.There was no significant difference between the patients and controls with regard to the average serum level of eotaxin.After treatment with NB-UVB,the serum levels of TARC,CTACK and MDC,but not eotaxin,significantly decreased in the patients.The total clinical effectiveness rate was 76.36％,and the accumulated SCORAD points and VAS scores decreased significantly. Conclusions NB-UVB is able to down-regulate significantly the serum levels of TARC,CTACK and MDC.It can affect immune function and regulate any imbalance of Th1/Th2 cells.This might be one of the mechanisms of NB-UVB treatment for AD.The clinical data demonstrate that NB-UVB is a safe and effective treatment for AD. Key words: Dermatitis, atopic ; Ultraviolet therapy; Chemotactic factors

O1 Chemokine and chemokine receptor analysis reveals elevated IP-10 levels and increased number of CCR5+ and CXCR3+ CD4 T cells in synovial fluid of patients with JIA

Background: Chemokines and their receptors are important elements for the selective attraction and activation of various subsets of leukocytes. Expression of CXCR3 ligands, such as monokine induced by IFN-γ (Mig) leads to preferential Th1 recruitment, whereas CCR4 ligands, thymus and activation regulated chemokine (TARC) or macrophage derived chemokine (MDC), mediate preferential Th2 recruitment. Although atopic dermatitis (AD) has been shown to be a Th2-type disease, recent studies have revealed that Th1-type cytokines, such as IFN-γ, especially in chronic skin lesions, play important roles in pathogenesis of AD. Objective: The purpose of this study was to investigate serum levels of Th2 chemokines TARC and MDC and a Th1 chemokine Mig in the same samples from patients with AD and their clinical correlation. Methods: Serum chemokine levels in patients with AD (n=55), contact dermatitis (CD; n=15), and normal controls (n=30) were examined by ELISA. Results: Serum levels of TARC and MDC in AD patients and CD patients were significantly higher than those found in normal controls. Serum levels of these chemokines were similar for AD patients and CD patients. Furthermore, these levels correlated positively with disease severity, total IgE levels, and peripheral eosinophilia in AD patients. Serum Mig levels in AD patients and CD patients were significantly higher than those in control subjects. However, serum Mig levels were significantly elevated in CD patients relative to AD patients. Furthermore, serum Mig levels correlated positively with levels of both TARC and MDC in AD patients. Conclusion: These results suggest that both Th2 and Th1 chemokines may play roles in the development of AD.

Chemokines Indicate Allergic Bronchopulmonary Aspergillosis in Patients with Cystic Fibrosis

Allergic bronchopulmonary aspergillosis (ABPA) is characterized by a Th2 immune response. Mouse models suggest a critical role for the Th2 chemokines thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) in ABPA. To determine whether serum levels of TARC and MDC characterize ABPA in patients with cystic fibrosis (CF) and to examine longitudinally if levels of TARC and MDC indicate ABPA exacerbations in patients with CF. Levels of TARC and MDC and levels of Th1 (IL-12 and IFN-gamma) and Th2 (IL-4, IL-5, and IL-13) cytokines were analyzed in serum of 16 patients with CF with ABPA, six non-CF patients with asthma with ABPA, 13 patients with CF colonized with Aspergillus fumigatus, six patients with CF sensitized to A. fumigatus, 12 atopic patients with CF, and 13 non-CF atopic control subjects by ELISA. The longitudinal course of TARC, MDC, and IgE levels was assessed during ABPA episodes. Patients with ABPA had significantly higher serum levels of TARC compared with the other patient groups. Cytokine levels did not differ among the patient groups. Longitudinally, levels of TARC indicated ABPA exacerbations in patients with CF more clearly than IgE levels. In patients with CF and ABPA, levels of TARC correlated positively with specific IgE to A. fumigatus and rAsp f4. Serum levels of TARC differentiate patients with CF or patients with asthma with ABPA from patients with CF colonized with or sensitized to A. fumigatus, atopic patients with CF, and atopic control subjects. Longitudinally, levels of TARC indicate ABPA exacerbations, suggesting TARC as a marker for identification and monitoring of ABPA in patients with CF.

Serum thymus and activation‐regulated chemokine, macrophage‐derived chemokine and eotaxin as markers of severity of atopic dermatitis

Expression of CCR4 ligands, such as thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC), leads to preferential influx of T-helper (Th) 2-type lymphocytes to the lesional skin in atopic dermatitis (AD). Eotaxin, like the CCR3 ligand, is an important contributor of eosinophils recruitment in the course of AD. These chemokines are assumed to play an important role in the pathomechanism of AD. In this study, the serum concentration of TARC, MDC, eotaxin and total immunoglobulin E (IgE) in AD patients and healthy people were compared. Correlation between the studied indices and activity of AD was established. Severity of AD was assessed according to the SCORAD score. The study comprised 44 healthy people and 43 patients with AD. The serum concentrations of TARC, MDC, eotaxin and IgE were measured with the use of enzyme-linked immunosorbent assay kits. The serum levels of TARC, MDC, eotaxin and IgE appeared to be significantly higher in patients with AD than in healthy people. A strong positive correlation was revealed between the levels of TARC, MDC, total IgE in serum of patients with AD and SCORAD. In contrast, no significant relationship was found for the serum eotaxin concentration and TARC, MDC, IgE or disease severity. Our findings indicate that TARC and MDC are actively involved in the pathogenesis of AD and their expression, opposite to that of eotaxin, is strongly associated with clinical picture of atopic dermatitis.

Both Th2 and Th1 chemokines (TARC/CCL17, MDC/CCL22, and Mig/CXCL9) are elevated in sera from patients with atopic dermatitis

Background : Chemokines and their receptors are important elements for the selective attraction and activation of various subsets of leukocytes. Expression of CXCR3 ligands, such as monokine induced by IFN-γ (Mig) leads to preferential Th1 recruitment, whereas CCR4 ligands, thymus and activation regulated chemokine (TARC) or macrophage derived chemokine (MDC), mediate preferential Th2 recruitment. Although atopic dermatitis (AD) has been shown to be a Th2-type disease, recent studies have revealed that Th1-type cytokines, such as IFN-γ, especially in chronic skin lesions, play important roles in pathogenesis of AD. Objective : The purpose of this study was to investigate serum levels of Th2 chemokines TARC and MDC and a Th1 chemokine Mig in the same samples from patients with AD and their clinical correlation. Methods : Serum chemokine levels in patients with AD ( n=55), contact dermatitis (CD; n=15), and normal controls ( n=30) were examined by ELISA. Results : Serum levels of TARC and MDC in AD patients and CD patients were significantly higher than those found in normal controls. Serum levels of these chemokines were similar for AD patients and CD patients. Furthermore, these levels correlated positively with disease severity, total IgE levels, and peripheral eosinophilia in AD patients. Serum Mig levels in AD patients and CD patients were significantly higher than those in control subjects. However, serum Mig levels were significantly elevated in CD patients relative to AD patients. Furthermore, serum Mig levels correlated positively with levels of both TARC and MDC in AD patients. Conclusion : These results suggest that both Th2 and Th1 chemokines may play roles in the development of AD.

Variations in the human Th2-specific chemokine TARC gene.

Th2-specific chemokine thymus and activation-regulated chemokine (TARC)/CC chemokine ligand (CCL)17 is highly implicated in the pathogenesis of Th-2-dominated allergic diseases such as bronchial asthma (BA) and atopic dermatitis (AD). We performed polymorphism screening of the coding and promoter regions of the TARC gene. We found two rare variations in the coding region of exon 3 (2134C>T and 2037G>A) and a single nucleotide polymorphism (SNP) in the 5'-flanking region (-431C>T). Individuals carrying the 431T allele showed significantly increased serum levels of TARC compared with those not carrying the 431T allele, suggesting that this SNP has functional significance. However, when the genotypes at the SNP site were determined for 158 healthy individuals, 105 patients with BA and 148 patients with AD, we observed no significant association of the SNP with susceptibility to BA or AD.