Serum Thymus And Activation-regulated Chemokine Levels Research Articles

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.

The role of thymus and activation-regulated chemokine as a marker of severity of atopic dermatitis

The role of thymus and activation-regulated chemokine as a marker of severity of atopic dermatitis

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.

Two cases of eczematous eruptions caused by everolimus

AbstractObjectiveEverolimus, an inhibitor of the mammalian target of rapamycin, has been used in the treatment of several types of tumor. Erythematous maculopapular and acneiform rashes are the major dermatological adverse events associated with everolimus therapy, but we encountered two cases of eczematous eruption caused by everolimus.MethodWe assessed the clinical features and laboratory findings of the two cases.ResultsA 52‐year‐old woman and a 59‐year‐old man developed pruritic papules and erythema over their entire bodies after initiation of everolimus therapy. Both patients exhibited peripheral eosinophilia and increased serum thymus and activation‐regulated chemokine (TARC) levels. A skin biopsy from one patient revealed the features of chronic dermatitis. Both the skin manifestations and the pruritis disappeared rapidly after the discontinuation of everolimus treatment. The peripheral blood eosinophil and serum TARC levels also decreased.ConclusionEczematous eruption associated with an elevated serum TARC level is a dermatological event associated with everolimus therapy.

Plasma Thymus and Activation-Regulated Chemokine (TARC) As Diagnostic Marker in Pediatric Hodgkin Lymphoma

BackgroundPediatric classical Hodgkin lymphoma (cHL) is a clonal disorder in an inflammatory background, also known as the microenvironment. This microenvironment is of major importance for growth and survival of the malignant Hodgkin/Reed Sternberg (HRS) cells. HRS cells and the microenvironment communicate through chemo- and cytokines. Blood biomarkers result from this active crosstalk, and may be a surrogate for lymphoma viability (Steidl et al, JCC 2011). Blood biomarkers are important because they hold the promise to be easily available and cost-effective. One promising biomarker in adult patients with cHL is the “Thymus and Activation-Regulated Chemokine, TARC (Plattell et al, Haematologica 2012). Elevated TARC levels are also described in patients with atopic dermatitis (Hijnen et al, J All Clin Immunol 2004).In adult cHL patients about 85% of patients have significantly elevated levels of TARC in pre-treatment serum or plasma compared to healthy controls (Plattell et al).So far nothing is known about TARC in pediatric cHL patients. To define its value as a diagnostic marker in pediatric cHL patients, we compared TARC levels of pediatric cHL patients with control patients. This study was IRB-approved and registered under Dutch Trial registry number 6876.MethodsAfter providing informed consent, plasma and serum samples were collected of newly diagnosed cHL patients before start of treatment. To define normal values of TARC in children, samples were collected from non-cHL randomly selected patients from the hematology, endocrinology and oncology outpatient clinic. Baseline characteristics including history of atopic dermatitis were collected. These control patients were divided in three age groups (0-9,10-14 and 15-18 years). TARC levels were measured by enzyme-linked immunosorbent assay (R&D systems, Human CCL17/TARC Quantikine ELISA Kit). TARC levels of the cHL patients were compared to the control group to obtain ROC curves and calculate the AUC, cross-validated sensitivity and specificity and accuracy of TARC as a diagnostic marker. We hypothesized that pediatric cHL patients had elevated pretreatment TARC levels in both serum and plasma. Analyses were done using SAS V9.4.ResultsFourteen cHL patients were included with a median age of 14 (range 11-17) years. Ten (71.4%) were female. Eighty patients were included in the control group with a median age of 12 (range 10 months-18) years. Twenty-nine patients (36.3%) were included in age group 0-9, 25 (31.2%) in age group 10-14 and 26 (32.5%) in age group 15-18. Thirty-nine (48.8%) were female.Patients of the control group had a median TARC value of 71 (range 18-762) pg/ml for plasma and 318 (range 27-1300) pg/ml for serum. TARC plasma and serum levels decreased with age (Spearman correlation -0.26, 2-tailed p=0.0204), but there were no statistically significant pairwise comparisons found between the pre-specified age groups. In the eight control patients (10%) with atopic dermatitis no significantly higher plasma and serum levels were found (plasma median with eczema 97 versus 70 pg/ml without eczema (p=0.71) and serum median with eczema 643 versus 317 pg/ml (p=0.71)).Plasma was collected in 14 cHL patients, and all had elevated TARC levels, with a median plasma level of 18449 (range 1635-55821) pg/mL. Serum samples were collected in 8/14 cHL patients and all had elevated serum TARC levels. Median serum level: 46703 (range 12817-149739) pg/ml.The plasma TARC levels of cHL patients were significantly higher than those of the control group patients (p<0.001). With a cut-off of level of of 898.70 pg/ml, we obtained 100% (95% CI 73% - 100%) sensitivity and 100% (95% 94% - 100%) specificity. Serum TARC levels also were significantly higher than those of the control group patients (p<0.001), with a cut-off level of 10283.57 pg/ml, sensitivity and specificity will be 100% (95% CI 60% - 100% for sensitivity and 95% CI 94% - 100% for specificity).ConclusionAll classical cHL patients had significantly higher TARC levels compared to the 80 control patients. Despite the small sample size of cHL patients, TARC was found to be a sensitive and specific diagnostic marker for pediatric cHL in both plasma and serum. Further research with a bigger sample of cHL patients is necessary to improve the accuracy of the sensitivity, as well as to investigate whether TARC is also a valuable marker for disease response during treatment in pediatric patients with cHL. DisclosuresNo relevant conflicts of interest to declare.

Alteration of serum thymus and activation-regulated chemokine level during biologic therapy for psoriasis: Possibility as a marker reflecting favorable response to anti-interleukin-17A agents.

Biologics show great efficacy in treating psoriasis, a chronic inflammatory skin disease. The high cost and side-effects of biologics, dose-reduction, elongation of administration interval and suspension are possible options. However, there has been no reliable biomarker we can use when we consider these moderations in therapy. This study was conducted to test the possibility of using serum thymus and activation-regulated chemokine (TARC) level as an indicator for step down of biologic therapy. Serum TARC level was measured in 70 psoriatic patients at Asahikawa Medical University, and a correlation of TARC and severity of skin lesions was analyzed. Referring to serum TARC level, psoriatic patients can be divided into two groups. One is a population in which serum TARC level is positively correlated with severity of skin lesions, and the other is a population with low psoriatic severity and high TARC level. Serum TARC level was higher in the group that achieved PASI-clear with biologics than in the group which did not achieve PASI-clear. Among biologics, the group treated with secukinumab, an anti-interleukin (IL)-17A agent, showed significantly higher TARC level compared with the group treated with anti-tumor necrosis factor agents. In certain populations achieving PASI-clear, serum TARC level may be a potent marker reflecting better response to IL-17A inhibitors, and in this case step down of treatment for psoriasis is possible.

Anti-inflammatory effect of collagen tripeptide in atopic dermatitis

BackgroundAtopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease in which type 2 allergic inflammation plays an important role. Collagen tripeptide (CTP) is a functional collagen fraction with a high content of Gly-X-Y tripeptides. ObjectiveTo examine the effect of CTP on inflammation in AD. MethodsLevels of inflammatory cytokines and chemokines, such as thymus- and activation-regulated chemokine (TARC), macrophage-derived chemokine, and thymic stromal lymphopoietin (TSLP), were examined in human keratinocytes supplemented with or without CTP under AD-like inflammation. To evaluate the functional effect of CTP, a migration assay was performed using the supernatants of cultured keratinocytes treated with CTP. The signaling pathway for CTP inhibitory activity was also determined. Additionally, we conducted a clinical trial with seventeen AD patients who were assigned randomly to receive daily for 12 weeks either 3.9g of a CTP product or normal collagen peptides (CP). The eruption area, severity scoring of atopic dermatitis (SCORAD), skin hydration, transepidermal water loss (TEWL), and itching score were evaluated. The levels of TARC, serum IgE, lactate dehydrogenase, and eosinophil counts at week 12 were also compared with those at the start of administration. ResultsIn human keratinocytes, TARC and TSLP mRNA and protein levels were inhibited significantly by CTP treatment under AD-like inflammation. Supernatants obtained from CTP-treated keratinocytes inhibited cell migration. STAT1 phosphorylation was significantly decreased by CTP in a dose-dependent manner. In the clinical trial, 13 patients (7 for CTP, 6 for CP) completed the study. The eruption area, SCORAD, and TEWL at week 12 were reduced significantly compared with the initial values in the CTP but not CP group. A significant reduction in the serum TARC level was observed only in the CTP group at week 12. Other blood parameters were not improved in either group. ConclusionCTP may have therapeutic benefit for AD by inhibiting type 2-skewed allergic inflammation.

Hydrogen water ameliorates the severity of atopic dermatitis-like lesions and decreases interleukin-1β, interleukin-33, and mast cell infiltration in NC/Nga mice.

Objectives:To examine the effect of hydrogen water (HW) on the severity of atopic dermatitis (AD) and elucidate the underlying pathophysiological mechanisms.Methods:For this experimental study between March 2015 and December 2015, NC/Nga mice characterized by mild AD severity were given either HW (n=11) or purified water (PW) (n=9) ad libitum; specific-pathogen-free mice (n=9) were used as AD-free control. Atopic dermatitis severity score and transepidermal water loss (TEWL) were examined at baseline (0 week), and after 4 weeks of HW/PW treatment. Levels of serum thymus and activation-regulated chemokine (TARC) and cytokines in the AD lesion were measured by ELISA; and mRNA expression of TARC and aquaporin (AQP-3) genes in the skin was examined by real-time polymerase chain reaction.Results:Mice treated with HW for 4 weeks demonstrated a significant decrease in the AD severity score compared with PW-treated mice (p<0.01). Hydrogen water administration also significantly reduced TEWL and serum TARC levels (p<0.01), infiltration of mast cells (p<0.05), and secretion of the proinflammatory cytokines interleukin (IL)-1β and IL-33 (p<0.05) in skin lesions compared with PW. However, no difference was observed between PW and HW groups in interferon-g secretion and expression of AQP-3 and TARC genes.Conclusion:Hydrogen water suppressed inflammation in AD mice, leading to amelioration of disease severity, which suggests the therapeutic potential of HW in AD treatment.

The thymus and activation-regulated chemokine (TARC) level in serum at an early stage of a drug eruption is a prognostic biomarker of severity of systemic inflammation

BackgroundIn severe drug eruptions, precise evaluation of disease severity at an early stage is needed to start appropriate treatment. It is not always easy to diagnose these conditions at their early stage. In addition, there are no reported prognostic biomarkers of disease severity in drug eruptions. The aim of this study was to test whether the thymus and activation-regulated chemokine (TARC) level in serum at an early stage of a drug eruption can serve as a prognostic biomarker of systemic inflammation. MethodsStudy participants included 76 patients who received a diagnosis of a drug eruption, one of the following: drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome, maculopapular exanthema, and erythema multiforme. Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) was eliminated in this study because scoring system for evaluating the severity was established. Correlation coefficients between serum TARC levels and indicators of systemic inflammation, including the neutrophil-to-lymphocyte ratio, Glasgow prognostic score, modified systemic inflammatory response syndrome (mSIRS) score, and C-reactive protein in serum were evaluated. ResultsSerum TARC levels positively correlated with the neutrophil-to-lymphocyte ratio, Glasgow prognostic score, mSIRS score, C-reactive protein, albumin, white blood cell count, body temperature, and pulse rate. TARC levels negatively correlated with systolic blood pressure. Among these parameters, the mSIRS score showed strong correlation (correlation coefficient: 0.68). ConclusionsSerum TARC levels correlate well with indicators of systemic inflammation and of disease severity among patients with a drug eruption except SJS/TEN. Serum TARC may be a prognostic biomarker of severity of inflammation in drug eruptions.

The Relationship Between Serum TARC, TSLP and POSTN Levels and Childhood Atopic Dermatitis.

The aim of the study is to evaluate the relationship between serum periostin (POSTN), thymus and activation-regulated chemokine (TARC), and thymic stromal lymphopoietin (TSLP) levels and disease severity and atopy in children with atopic dermatitis. Sixty children with atopic dermatitis and 31 healthy controls were included in the study. The disease severity was measured by SCORAD scores. Serum POSTN, TARC, and TSLP levels were measured in all participants. The demographic data were recorded, and skin prick tests were performed to evaluate atopy in children with atopic dermatitis. Serum POSTN, TARC, and TSLP levels were higher in children with atopic dermatitis than in healthy children (p = 0.041, p = 0.034, and p < 0.001, respectively). Serum POSTN levels were higher with atopy than without atopy in children with atopic dermatitis (p = 0.047). There was a positive moderate correlation between POSTN and the age and symptom duration in children with atopic dermatitis (r = 0.343, p = 0.007, r = 0.484, and p < 0.0001, respectively). In receiver operating characteristics (ROC) analysis, the area under the curve (AUC) was 0.789 (95% CI (0.694 - 0.883), p < 0.0001) for TSLP and the AUC was 0.636 (95% CI (0.522 - 0.750), p = 0.034) for TARC to predict severe atopic dermatitis. Serum POSTN, TARC, and TSLP were higher in children with atopic dermatitis. Serum TARC and TSLP levels might be used as biomarkers to predict severe atopic dermatitis and serum POSTN to predict atopy and disease chronicity.

Serum TARC levels are strongly correlated with blood eosinophil count in patients with drug eruptions

BackgroundThis study aims to evaluate the relationship between serum thymus and activation-regulated chemokine (TARC) levels with various clinicopathological conditions in patients with drug eruptions. The value of TARC in diagnosing drug-induced hypersensitivity syndrome (DIHS) was also examined. MethodsStudy participants included 84 patients who presented with generalized eruptions suspected to be drug-related, including DIHS, Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), maculopapular exanthema (MPE), erythema multiforme (EM), erythroderma, and toxicoderma. The correlation coefficients between serum TARC levels and clinical parameters in peripheral blood samples were calculated. ResultsSerum TARC levels in patients with DIHS were higher than those found in patients with SJS/TEN, MPE, EM, and toxicoderma. TARC levels had 100% sensitivity and 92.3% specificity in diagnosing DIHS, with a threshold value of 13,900 pg/mL. Serum TARC levels positively correlated with age, white blood cell (WBC) count, neutrophil count, eosinophil count, monocyte count, atypical lymphocyte (Aty-ly) count, serum blood urea nitrogen (BUN) levels, and creatinine (Cr) levels. It negatively correlated with serum total protein (TP), albumin (Alb), and estimated glomerular filtration rate (eGFR). Among these clinical parameters, blood eosinophil counts were most strongly correlated with serum TARC levels, with a correlation coefficient of 0.53. ConclusionsSerum TARC levels are well correlated with blood eosinophil counts in patients with generalized drug eruptions, indicating that Th2-type immune reactions underlie TARC production. Serum TARC measurements also have potent diagnostic value for DIHS, with high sensitivity and specificity.

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.

Study of pruritus in chronic hepatitis C patients

To investigate the occurrence and severity of pruritus in chronic hepatitis C patients treated with or without interferon (IFN) therapy. A total of 89 patients with chronic hepatitis C and 55 control (non-hepatitis) patients were asked to rate their experience of diurnal and nocturnal pruritus in the preceding week using a visual analogue scale (VAS) and a five-point scale, respectively. Blood samples were taken and serum thymus and activation-regulated chemokine (TARC) levels were measured by enzyme-linked immunosorbent assay. A significantly greater proportion of chronic hepatitis C patients experienced nocturnal pruritus compared with control (58.4% vs 5.5%, P < 0.0001). Chronic hepatitis C patients also had more severe pruritus compared with control patients, indicated by the higher mean VAS scores in both the IFN-treated and non-IFN-treated groups. In particular, patients who received combined peginterferon alfa-2b and ribavirin had significantly higher mean VAS scores than those receiving peginterferon alfa-2a or no IFN treatment. Serum TARC levels did not correlate with pruritus scores, and no significant differences in TARC levels were observed between the IFN-treated and non-IFN-treated groups. Patients with chronic hepatitis C experience pruritus more than those without. Serum TARC levels do not correlate with pruritus severity in chronic hepatitis C patients.

Decrease of Serum TARC Levels As Predictive Biomarkers of Response to Targeted Therapy with Kinase Inhibitors in Refractory/Relapsed Hodgkin Lymphoma Patients

INTRODUCTION: Identification of predictive biomarkers of response to new agents represents a challenging issue. Thymus and Activation-Regulated Chemokine (TARC) is a protein highly expressed by Reed-Sternberg cells in Hodgkin lymphoma (HL) and has been demonstrated to be a prognostic biomarker in HL patients treated with chemotherapy. We investigated the correlation between clinical response and early variation of serum TARC levels in patients with refractory/relapsed HL treated with kinase inhibitors. Patients were enrolled in two consecutive phase II trials evaluating activity and safety of the multikinase inhibitor Sorafenib (Nexavar®, Bayer) used as single agent, or in combination with the AKT inhibitor Perifosine (Æterna Zentaris GmBH, Germany).METHODS: Between July 2008 and November 2011, 30 patients (19 males and 11 females; median age 30 years, range, 17-73 years) with relapsed (n = 3) or refractory (n = 27) HL were analyzed. In one trial, patients received Sorafenib alone (400 mg BID, per os), and in the second trial Perifosine (50 mg BID, per os) for 4 weeks followed by combination therapy of Perifosine plus Sorafenib (400 mg BID, per os) until disease progression or clinically significant toxicity. Tumor responses were assessed according to the revised response criteria for malignant lymphoma of the International Working Group. Serum samples collected prior to therapy initiation and monthly thereafter were analyzed for TARC by ELISA. Early variation in TARC levels was calculated as percentage difference between values at baseline and at day 60 after starting therapy. Comparison of variation of TARC between different groups of patients was calculated using the Mann-Whitney Test, correlation between clinical response and TARC reduction was calculated using Fisher’s exact text and presented also as relative risk (RR). The study was approved by the Institutional Ethical CommitteeRESULTS: Nine out of 30 patients (30%) achieved clinical responses, including complete response (CR, n = 1) and partial response (PR, n = 8), 12/30 patients achieved stable disease (SD), and 9/30 patients experienced progressive disease (PD). Median overall survival (OS), progression-free survival (PFS) and duration of response (DOR) were 18, 4.5 and 3 months, respectively. Data of TARC at baseline and during therapy were available for all 30 patients but only 29 patients were evaluated. The patient achieving CR who showed baseline and 60-day values below 500 pg/ml (212 pg/ml and 368 pg/ml, respectively) was in fact excluded from analysis. At baseline, the median TARC level for the whole population was 13451 pg/ml (range, 1010 - 89877). No differences in baseline TARC levels were detected between patients achieving PR, SD and PD as best response. The median percentage variation of TARC levels after 60 days of therapy in PR, SD and PD patients was -57% (IQ range, -79% to -28%), -15% (IQ range, -78% to +8%) and +6% (IQ range, -49% to >100%). Variation of TARC observed among PR patients was significantly different from variation detected in PD group (p=0.005), whereas no differences were observed between PR and SD patients. A decrease of TARC levels at day 60 was observed in 17 patients, median percentage reduction was 49% (range, 8% – 94%). TARC reduction discriminated patients sensitive to treatment, in fact 15/17 patients (88%) with evidence of a reduction achieved PR (n=7) or SD (n=8), whereas 7/12 patients showing no change or increasing values of TARC experienced PD (p=0.014). The chance of obtaining PR and SD was greater in patients with evidence of TARC reduction than in patients with stable or increasing values (RR 3.37, 95%CI, 0.97 – 11.7). When we considered the median percentage reduction of 49% as cut-off, this value didn’t discriminate PR from SD patients. Similarly, deeper reduction in TARC levels was not correlated to longer PFS or DOR in responding patients.CONCLUSIONS: Analysis of TARC in HL patients treated with perifosine and sorafenib allowed to identify a biomarker predicting response to treatment with kinase inhibitors. Early reduction of TARC seems to be a useful tool for selecting patients who will receive a clinical benefit from therapy. However, correlation observed between early reduction and clinical response need to be validated in larger studies. DisclosuresNo relevant conflicts of interest to declare.

Expression of thymus and activation-regulated chemokine (TARC) by human dermal cells, but not epidermal keratinocytes

BackgroundSerum levels of thymus and activation-regulated chemokine (TARC/CCL17) have served as a reliable biomarker of disease progression of atopic dermatitis (AD). However, it remains to be scientifically explained why serum TARC levels correlate well with the degree of AD progression. ObjectiveWe hypothesized that dermal cells, but not epidermal keratinocytes, are major cellular sources of TARC and thus responsible for subclinical skin inflammation. This study aimed to identify the skin cells that can produce TARC protein. MethodsPrimary normal human epidermal keratinocytes (NHEK), dermal microvascular endothelial cells (HMVEC-dBl) and dermal fibroblasts (NHDF) were stimulated with TNF-α and IL-4, alone and in combination. TARC mRNA and protein levels were quantified by qPCR and ELISA, respectively. We also investigated the effects of such immunosuppressants as a corticosteroid (dexamethasone) and tacrolimus (FK506) on TARC production, and used various signaling inhibitors to evaluate the signaling pathways involved in TARC expression. ResultsAlthough neither TNF-α nor IL-4 alone induced TARC production by any of the tested cell types, together they induced expression of TARC mRNA and appreciable amounts of TARC protein by HMVEC-dBl and NHDF, but not by NHEK. TARC production by those dermal cells was not inhibited by dexamethasone or FK506. TARC production by HMVEC-dBl was completely inhibited by NF-κB and p38 MAPK inhibitors, but not by an ERK inhibitor. ConclusionDermal cells, but not epidermal keratinocytes, may be important cellular sources of TARC in AD skin. Therefore, even if epidermal eczematous lesions seem to be improved, complete inhibition of inflammation in the dermis is thought to be particularly important for suppressing both the TARC blood level and progression of AD. However, immunosuppressants did not directly inhibit TARC production by the dermal cells. Anti-inflammatory therapy may decrease TARC blood levels in AD patients indirectly, via its inhibitory effects on TNF-α- and/or IL-4-producing cells in the dermis.

Variations in Serum TARC and I-TAC Levels Reflect Minor Changes in Disease Activity and Pruritus in Atopic Dermatitis

Atopic dermatitis (AD) is a chronic or relapsing inflam-matory skin disease. Scratching in AD patients results in proinflammatory cytokine and chemokine production. Thus, serum levels of monocyte chemotactic protein-1 (MCP-1), regulated on activation, normal T-cell expressed and secreted (RANTES ), macrophage inflammatory pro-tein (MIP)-1β, eotaxin, thymus and activation-regulated chemokine (TARC), and macrophage-derived chemokine (MDC) were increased in AD patients, compared with normal controls (1–4). With regards to Th1 chemokines such as interferon (IFN)-γ-inducible protein 10 (IP-10), IFN-γ-inducible T-cell α-chemoattractant (I-TAC), and monokine induced by IFN-γ (MIG), their expression in le-sional AD skin was confirmed by immunohistochemistry ±(5). They may negatively contribute to the development of AD because macrophages from AD patients produced lower levels of IP-10 compared to cells from healthy con -trols in response to α-toxin (6) and the expression of MIG and IP-10 was lower in Langerhans cells from patients with AD than from patients with psoriasis, whereas the opposite was observed for TARC and MDC (7).Visual analogue scale (VAS) is a valuable method to assess pruritus intensity in patients with pruritic der-matoses (8). In this study , we focus on temporal variation of pruritus in each patient and compare serum samples taken at different time points when there were only slight, if any, changes in disease activity. The aim of this study was to highlight the most sensitive chemokine associated with changes in pruritus in AD patients. MATERIALS AND METHODS

English

Serum thymus and activation-regulated chemokine (TARC) levels are associated with the disease activity of patients with atopic dermatitis (AD) and sensitively reflect short-term changes in skin conditions. The main treatment for AD is topical agent application. This study investigated the relationship between serum TARC levels and the dosage of topical agents, including corticosteroids and/or tacrolimus, in patients with AD. The serum TARC levels of 56 AD patients and the amounts of topical agents prescribed to them were investigated retrospectively. The weekly reduction in serum TARC levels and weekly dosage of topical agents among AD patients were compared and their associations were evaluated. The dosage of topical agents was closely related to serum TARC levels. One gram of strong rank steroid or the equivalent amount of steroid/tacrolimus is required to reduce serum TARC levels by 9.94 pg/mL weekly in moderate to severe AD patients. Higher initial TARC levels require more topical agent, which results in a more rapid decrease in TARC levels. The serum TARC levels and eosinophil numbers in peripheral blood are significantly correlated. Serum TARC level improvement and topical agent dosage are strongly correlated. TARC and eosinophil numbers are significantly correlated, but the wider range of TARC levels seems to be clinically more useful for monitoring AD severity. The serum TARC level is a very sensitive biomarker for monitoring the severity and treatment response in AD.

Saussurea lappa alleviates inflammatory chemokine production in HaCaT cells and house dust mite-induced atopic-like dermatitis in Nc/Nga mice

Saussurea lappa is a traditional herbal medicine used for to treat various inflammatory diseases. In this study, we investigated the protective effects of S. lappa against atopic dermatitis using human keratinocyte HaCaT cells, murine mast cell line MC/9 cells, and a house dust mite-induced atopic dermatitis model of Nc/Nga mice. Treatment with the S. lappa caused a significant reduction in the mRNA levels and production of inflammatory chemokines and cytokine, including thymus- and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), regulated on activation, normal T-cell expressed and secreted (RANTES), and interleukin-8 (IL-8) in tumor necrosis factor-α/interferone-γ-stimulated HaCaT cells. S. lappa exhibited the significant reduction in histamine production in MC/9 cells. In the atopic dermatitis model, S. lappa significantly reduced the dermatitis score and serum IgE and TARC levels. In addition, the back skin and ears of S. lappa-treated Nc/Nga mice exhibited reduced histological manifestations of atopic skin lesions such as erosion, hyperplasia of the epidermis and dermis, and inflammatory cell infiltration. In conclusion, an extract of S. lappa effectively suppressed the development of atopic dermatitis, which was closely related to the reduction of chemokines and cytokine. Our study suggests that S. lappa may be a potential treatment for atopic dermatitis.

Correlation between serum thymus and activation-regulated chemokine levels and stratum corneum barrier function in healthy individuals and patients with mild atopic dermatitis

Serum thymus and activation-regulated chemokine (TARC) levels closely reflect the disease activity of atopic dermatitis (AD). AD is characterized by impaired epidermal barrier function and atopic dry skin. However, dry skin is also a very common problem in healthy individuals. To investigate the relationship between serum TARC levels and epidermal barrier function in healthy subjects and patients with mild AD. This study included 2 groups, 121 healthy subjects (healthy group) and 66 patients with mild AD (mild AD group). Barrier function was assessed by transepidermal water loss (TEWL) and stratum corneum hydration (SCH). Significantly elevated serum TARC levels and TEWL values and significantly decreased SCH values were detected in the mild AD group compared to those in the healthy group. In the mild AD group, serum TARC levels were significantly correlated with TEWL values and were inversely correlated with SCH values. Importantly, serum TARC levels were also inversely correlated with SCH values in the healthy controls. TEWL values in the healthy group tended to be correlated with TARC levels but did not reach statistical significance. Together with TEWL and SCH, serum TARC level is a useful biomarker, reflecting impairment of epidermal function in AD patients as well as healthy subjects.