Activation-regulated Chemokine Levels Research Articles

Ameliorative Effect of Topical Clinoptilolite on 2,4- Dinitrof luorobenzene Induced Atopic Dermatitis Model in Mice

Atopic dermatitis is a multifactorial disease process. It is defined as "a genetically predisposed inflammatory and itchy allergic skin disease associated with the production of immunoglobulin E against environmental allergens". Experimental models are considered important in the evaluation of therapeutic agents for the treatment of atopic dermatitis. This study aimed to reveal the effects of clinoptilolite and tacrolimus on atopic dermatitis lesions in the atopic dermatitis model in mice induced with 2,4-dinitrofluorobenzene. For inducing the atopic dermatitis model, mice were administered topically on the back with 0.15% 2,4-dinitrofluorobenzene twice a week for 5 weeks. For the next 4 weeks, 0.15% 2,4-dinitrofluorobenzene was applied once a week to maintain inflammation. Afterward, topical tacrolimus cream (0.1%) and topical clinoptilolite powder were used for 4 weeks. Clinical score, serum thymus and activation-regulated chemokine, histopathology, and thymic stromal lymphopoietin (TSLP) immunostainings were evaluated between groups. While clinoptilolite treatment was found to be effective in the normalization of clinical scores, serum thymus and activation regulated chemokine levels were found to be variable and insignificant. Histopathologically, clinoptilolite had an ameliorative effect on epidermal thickness and inflammation yet there was no significant difference of mast cells and fibrosis between groups. Furthermore, clinoptilolite had an inhibitory effect of TSLP immunostaining on epidermal tissue. In conclusion, clinoptilolite could be an alternative treatment of atopic dermatitis with its effects similar to tacrolimus.

Clinical Course and Factors Correlated with Severe Morbidity and Mortality in Patients with Coronavirus Disease 2019 Undergoing Maintenance Dialysis in Kanagawa, Japan

Objective Patients undergoing maintenance dialysis are at a higher risk of morbidity and mortality due to severe coronavirus disease 2019 (COVID-19) than the general population. However, longitudinal data regarding this subpopulation of patients are lacking. We therefore examined the prognosis of patients with COVID-19 undergoing maintenance dialysis between 2020 and 2023. In addition, we explored the factors correlated with COVID-19 severity, focusing on the transition thereof throughout the observational period. Methods The primary outcome was the progression to severe or fatal COVID-19. We evaluated the correlation between the primary outcome and baseline demographic and clinical characteristics of patients. Patients undergoing maintenance dialysis who were hospitalized for mild-to-moderate COVID-19 between February 2020 and April 2023 were enrolled at four institutions in Kanagawa, Japan. Results Of the 173 patients, 7 (4.0%) developed severe COVID-19, and 12 (6.9%) died. The severe/death cohort was significantly older, with a higher percentage of unvaccinated patients than the non-severe cohort (58.2% and 25.0%, respectively; p=0.016). Thymus and activation-regulated chemokine levels on admission were lower in the severe/death cohort than in the non-severe cohort, albeit not to a statistically significant degree (148±84 mg/dL and 342±657 pg/mL, respectively; p=0.082). A multivariate logistic regression analysis revealed that the odds ratio for severe morbidity or death was 0.23 (95% confidence interval: 0.07-0.75) for vaccinated patients. Conclusion In patients undergoing maintenance dialysis, the severity rate of COVID-19 is approximately 10%. Vaccination was correlated with a reduced risk of severe COVID-19.

Successful Tezepelumab Response and the Usefulness of Serum TARC Level as a Biomarker in a Severe Type 2 Bronchial Asthma Patient After Dupilumab, Mepolizumab, and Benralizumab Failure

Background: Treatment for severe type 2 bronchial asthma (BA) has advanced rapidly with the development of biologics. However, research on the responders and biomarkers for each biologic remains limited. Case Presentation: A 64-year-old female non-smoker with eosinophilic chronic rhinosinusitis and severe type 2 BA was administered dupilumab due to worsening nasal obstruction and olfactory impairment. Following this, the patient experienced secondary eosinophilia and worsening asthma control, necessitating frequent administration of systemic corticosteroids. Additionally, widespread maculopapular exanthema developed. Consequently, the treatment was switched to mepolizumab, which reduced blood eosinophil count; however, asthma control did not improve, and the maculopapular exanthema worsened, prompting another change to benralizumab. Due to persistent inadequate asthma control, the treatment was subsequently switched to tezepelumab, which resolved the maculopapular exanthema and decreased asthma exacerbations. Additionally, improvements in forced expiratory volume in one second and the asthma control test score were observed, along with a reduction in the serum thymus and activation-regulated chemokine (TARC) level. Conclusions: In some patients with severe type 2 BA who experience secondary eosinophilia and worsening asthma control after dupilumab administration, tezepelumab can be effective, and serum TARC levels could serve as a biomarker.

Improved atopic dermatitis accompanied by pompholyx

In the treatment process of atopic dermatitis, pompholyx may occurs on palms and soles. However, there is limited knowledge about which patients are more likely to develop pompholyx and when it is expected to occur. Therefore, this study investigated the occurrence of pompholyx after the start of induction remission treatment. We collected medical information from 48 AD patients who visited Hiroshima University Hospital for the first time between January 2019 and December 2020, from the time of their first visit to 12 months later. In the initial group of 48 patients, 10 individuals developed pompholyx within 1 year after their first visit. There was no clear connection between the occurrence of pompholyx and treatment received. Most of the patients who developed pompholyx were above the age of 30. Serum thymus and activation-regulated chemokine (TARC) levels tended to be higher at the first visit in the group that later developed pompholyx compared to the group that did not. In conclusion, patients over the age of 30 with higher serum TARC levels may develop pompholyx while their AD is improving. It is crucial to provide these patients with information about the possibility of developing pompholyx during the course of their AD treatment and that it would be cured in the course of treatment.

Dupilumab treatment in children aged 6–11 years with severe atopic dermatitis is associated with reductions in serum immunoglobulin E and thymus and activation-regulated chemokine levels

Dupilumab treatment in children aged 6–11 years with severe atopic dermatitis is associated with reductions in serum immunoglobulin E and thymus and activation-regulated chemokine levels

Changes in eotaxin-3 and pulmonary and activation-regulated chemokine levels in patients after dupilumab treatment: a systematic review and meta-analysis.

Dupilumab is approved for a variety of type 2 inflammatory diseases. Changes in chemokine levels during treatment require further analysis. We evaluated changes in eotaxin-3 and PARC levels after dupilumab treatment through a meta-analysis, aiming to provide more comprehensive results. Databases were searched to select eligible publications. The study quality was assessed after inclusion. The standardized mean difference (SMD) was used for evaluation. Four studies were included. Eotaxin-3 levels were not seen significantly decreased at weeks 1 and 12, with SMD = -0.39 (95% CI: -1.78, 0.99) and -2.60 (95% CI: -5.77, 0.57), respectively (p > 0.05). Eotaxin-3 levels decreased significantly at weeks 2, 4, 8, 16, 24, 36, and 52, with SMD = -0.94 (95% CI: -1.61, -0.27); -1.17 (95% CI: -1.49, -0.84); -1.20 (95% CI: -1.52, -0.88); -1.31 (95% CI: -1.83, -0.79); -4.57 (95% CI: -6.90, -2.33); -5.28 (95% CI: -5.52, -5.04); and -4.03 (95% CI: -4.22, -3.85) (p < 0.05), respectively. PARC levels decreased significantly at weeks 4, 8, 12, and 16, with SMD = -1.08 (95% CI: -1.59, -0.58); -1.17 (95% CI: -1.68, -0.66); -1.11 (95% CI: -1.61, -0.60); and -1.15 (95% CI: -1.66, -0.64) (p < 0.05), respectively. Eotaxin-3 and PARC levels can be significantly reduced in patients treated with dupilumab.

Phenotype characterization and biomarker evaluation in moderate to severe type 2-high asthma.

There are two major pathological phenotypes of asthma, type 2 (T2)-high and T2-low asthma, which are important in determining treatment strategies. However, the characteristics and phenotypes of T2-high asthma have not yet been fully identified. This study aimed to identify the clinical characteristics and phenotypes of patients with T2-high asthma. This study used data from a nationwide asthma cohort study in Japan, NHOM Asthma Study. T2-high asthma was defined as a blood eosinophils count ≥ 300 /μL and/or fractional exhaled nitric oxide level ≥ 25 ppb, and the clinical characteristics and biomarkers were compared between T2-high and T2-low asthma. Furthermore, T2-high asthma was phenotyped via hierarchical cluster analysis using Ward's method. Patients with T2-high asthma were older, less likely to be female, had longer asthma duration, had lower pulmonary function, and had more comorbidities, including sinusitis and SAS. Patients with T2-high asthma showed higher serum thymus and activation-regulated chemokine and urinary leukotriene E4 levels and lower serum ST2 levels than those with T2-low asthma. There were four phenotypes among patients with T2-high asthma: Cluster 1 (youngest, early-onset, and atopic), Cluster 2 (long duration, eosinophilic, and low lung function), Cluster 3 (elderly, female-dominant, and late-onset), and Cluster 4 (elderly, late-onset, and asthma-COPD overlap-dominant). Patients with T2-high asthma have distinct characteristics and four distinct phenotypes, in which eosinophil-dominant Cluster 2 is the most severe phenotype. The present findings may be useful in precision medicine for asthma treatment in the future.

The influence of &lt;i&gt;Aspergillus fumigatus&lt;/i&gt; micromycetes on immune response regulation in patients with asthma

Introduction. Aspergillus fumigatus is able not only to sensitize patients with atopy, but also to colonize the respiratory tract, remaining a constant source of allergens due to the small spore size and thermal tolerance. Currently, the role of micromycetes in the immunopathogenesis of asthma has been poorly studied. The objective was to evaluate the features of the immune response regulation in patients with allergic bronchopulmonary aspergillosis (ABPA) or asthma with sensitization to A. fumigatus. Materials and methods. There were enrolled 15 patients with ABPA, 10 patients with asthma with sensitization to A. fumigatus, 16 patients with asthma without sensitization to A. fumigatus. The control group consisted of 16 apparently healthy volunteers. All patients underwent a clinical and functional examination. The subpopulations of blood lymphocytes were assessed by flow cytometry. The A. fumigatus allergen was added to peripheral blood samples to evaluate the production of IFN, IL-10 and IL-13. The serum cytokine levels in cell culture supernatants, as well as total IgE, A. fumigatus-specific IgE (sIgE) as well as thymus and activation-regulated chemokine (TARC) level were measured by enzyme-linked immunosorbent assay. Results. Significantly higher serum levels of total IgE, A. fumigatus-specific sIgE and TARC were found in patients with ABPA and asthma with sensitization to A. fumigatus compared to patients with asthma without sensitization to A. fumigatus. The results of lymphocyte immunophenotyping revealed significant excess of memory Th2 cells and T-regulatory cells in all patients with asthma compared to the control group. The count of Tfh2 was higher but memory Th17.1 cells were lower in patients with sensitization to A. fumigatus compared to those of apparently healthy volunteers. Patients with ABPA had significantly higher count of memory Th2 cells and TARC level compared to patients with asthma sensitized to A. fumigatus. The increased activity of memory Th2 cells is confirmed by increased secretion of IL-13 and IL-10 following along with decreased IFN production in response to specific fungal allergen stimulation of blood cells compared to the patients with asthma and the control group. A positive correlation was revealed between the count of memory Th2 cells and the levels of sIgE, IgE, TARC, a negative correlation with FEV1. Conclusion. Thus, exposure to A. fumigatus significantly enhances the activity of memory Th2 cells in patients with asthma which can lead to severe disease course and development of allergic bronchopulmonary aspergillosis. The features of the immune response identified dictate a need for a personalized approach to choose therapeutic tactics in such patients.

408 Dupilumab reduces biomarkers indicative of type 2 inflammation in children aged ≥ 6 months to 5 years with moderate-to-severe atopic dermatitis

Dupilumab was previously shown to reduce thymus and activation-regulated chemokine (TARC/CCL17) and total IgE levels in multiple type 2 inflammatory diseases, including atopic dermatitis (AD). Here, we assess the effects of dupilumab treatment on these biomarkers of type 2 inflammation in children aged 6 months – 5 years with moderate-to-severe AD. In LIBERTY AD PRE-SCHOOL (NCT03346434 part B), a phase 3, double-blind trial, children aged ≥ 6 months – 5 years with moderate-to-severe AD inadequately controlled with topical therapies were randomized 1:1 to subcutaneous dupilumab (200 mg if baseline weight ≥ 5 – < 15 kg, 300 mg if ≥ 15 – < 30 kg) or placebo every 4 weeks for 16 weeks.

Comparison of Acute Phase Thymus and Activation-Regulated Chemokine (TARC) Levels in Food Protein-Induced Enterocolitis Syndrome and IgE-Dependent Food Allergy.

Introduction: Patients with food protein-induced enterocolitis syndrome (FPIES) have elevated thymus and activation-regulated chemokine (TARC) levels in the acute phase. However, to the best of our knowledge, no study has evaluated TARC levels in the acute phase of immunoglobulin E-dependent food allergy (IgE-FA). If TARC elevation is a specific response to FPIES among FAs, TARC measurement may help distinguish between FPIES and IgE-FA. Thus, we investigated acute phase TARC levels in patients with FPIES and IgE-FA. Methods: Thirty-one episodes in 16 patients with FPIES and 20 episodes (13 were anaphylaxis) in 20 patients with IgE-FA were included. Patients with eczema were excluded. Serum TARC levels within 6 h of allergic reaction onset and age-adjusted TARC ratios (TARC levels divided by age-specific normal TARC values) were compared between the groups. Results: The median age was 1.1 and 3.6 years in the FPIES and IgE-FA groups, respectively (P < 0.001). The median (range) serum TARC (pg/mL) levels were significantly higher in the FPIES group than in the IgE-FA group [1,283 (410-3,821) versus 377 (109-1,539); P < 0.001]. The median (range) age-adjusted TARC ratios were also significantly higher in the FPIES group [2.56 (0.57-7.86) versus 1.08 (0.15-2.17); P < 0.001]. The area under the curve (AUC) for TARC to distinguish FPIES from IgE-FA was 0.926, and the AUC for the age-adjusted TARC ratio was 0.850. The odds ratio for FPIES diagnosis per 1,000 pg/mL increase in TARC was 31.6 (P = 0.002), and the odds ratio adjusted by age was 17.1 (P = 0.016). Conclusion: Acute phase TARC levels were higher in patients with FPIES than in patients with IgE-FA. The increase in acute phase TARC levels was considered to be a specific response to FPIES among FAs. Measurement of TARC levels in the acute phase may help differentiate FPIES from IgE-FA.

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.

297 Dupilumab reduces biomarkers indicative of type 2 inflammation in children aged ≥ 6 months to < 6 years with moderate-to-severe atopic dermatitis

Dupilumab was previously shown to reduce thymus and activation-regulated chemokine (TARC/CCL17) and total IgE levels in multiple type 2 inflammatory diseases, including atopic dermatitis (AD). Here, we assess the effects of dupilumab treatment on these biomarkers of type 2 inflammation in children aged 6 months – < 6 years with moderate-to-severe AD. In LIBERTY AD INFANT/PRE-SCHOOL (NCT03346434 part B), a phase 3, double-blind trial, children aged ≥ 6 months – < 6 years with moderate-to-severe AD inadequately controlled with topical therapies were randomized 1:1 to subcutaneous dupilumab (200 mg if baseline weight ≥ 5 – < 15 kg, 300 mg if ≥ 15 – < 30 kg) or placebo every 4 weeks for 16 weeks.

Bitter taste receptor T2R38 is expressed on skin-infiltrating lymphocytes and regulates lymphocyte migration

Bitter taste receptors (T2Rs) are G protein-coupled receptors involved in the perception of bitter taste on the tongue. In humans, T2Rs have been found in several sites outside the oral cavity. Although T2R38 has been reported to be expressed on peripheral lymphocytes, it is poorly understood whether T2R38 plays immunological roles in inflammatory skin diseases such as atopic dermatitis (AD). Then, we first confirmed that T2R38 gene expression was higher in lesional skin of AD subjects than healthy controls. Furthermore, skin T2R38 expression levels were correlated with serum thymus and activation-regulated chemokine and IgE levels in AD patients. In lesional skin of AD, section staining revealed that CD3+ T cells in the dermis were T2R38 positive. In addition, flow cytometry analysis showed T2R38 expression in skin T cells. Migration assays using T2R38-transduced Jurkat T cell leukemia cells revealed that T2R38 agonists exerted a dose-dependent migration inhibitory effect. Moreover, skin tissue extracts, as well as supernatants of cultured HaCaT keratinocytes, caused T2R38-dependent migration inhibition, indicating that there should be an endogenous ligand for T2R38 in the skin epidermis. These findings implicate T2R38 as a migratory inhibitory receptor on the skin-infiltrating lymphocytes and as a therapeutic target for allergic/inflammatory skin diseases.

Differences in Thymus and Activation-Regulated Chemokine and Squamous Cell Carcinoma Antigen 2 Levels in Food Protein-Induced Enterocolitis Syndrome and Atopic Dermatitis

Introduction: We previously reported that thymus and activation-regulated chemokine (TARC) levels measured after vomiting are useful predictors of a food protein-induced enterocolitis syndrome (FPIES) diagnosis. However, interpreting TARC levels in patients with eczema is difficult, as the levels are similarly elevated in patients with eczema caused by atopic dermatitis (AD). Therefore, we aimed to investigate whether it is possible to predict whether FPIES or AD is responsible for elevated TARC levels by simultaneously measuring TARC and squamous cell carcinoma antigen 2 (SCCA2), another T-helper type 2 biomarker. Methods: Twenty-one episodes in 11 patients with FPIES (FPIES group) and 42 age-matched patients with AD (AD group) were included in this study. Serum TARC and SCCA2 levels were measured, and those values and relative ratios were compared between groups. Results: The median age was 1.1 years in the FPIES group and 1.6 years in the AD group (p = 0.492). The median (interquartile range [IQR]) serum TARC concentration was significantly higher in the FPIES group than in the AD group (2,486 [1,815–4,097] pg/mL and 1,451 [1,201–1,751] pg/mL, respectively; p = 0.002). The median (IQR) SCCA2 concentration was significantly higher in the AD group than in the FPIES group (1.9 [1.3–2.9] pg/mL and 0.8 [0.6–1.5] pg/mL, respectively; p < 0.001). After matching, the analysis using stratified TARC values revealed no significant difference in TARC values between the FPIES and AD groups; however, the TARC/SCCA2 ratio was significantly higher in the FPIES group. Conclusion: Assessing the relative TARC/SCCA2 ratio may help predict whether elevated TARC levels measured after vomiting are caused by FPIES or AD.

Enhancing effect of sodium butyrate on phosphatidylserine-liposome-induced macrophage polarization.

Phosphatidylserine-containing liposomes (PSLs) can mimic the immunomodulatory effects of apoptotic cells by binding to the phosphatidylserine receptors of macrophages. Sodium butyrate, an antiinflammatory short-chain fatty acid, is known to facilitate the M2 polarization of macrophages. This study aimed to investigate the effect of sodium butyrate on PSLs-induced macrophage polarization. PSLs physical properties and cellular uptake tests, reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence staining, and flow cytometry analysis were performed to assess the polarization-related indicators of M1/M2 macrophages. The results showed that sodium butyrate did not affect the size and cellular uptake of PSLs. For M1 macrophage polarization, sodium butyrate significantly intensified the antiinflammatory function of PSLs, inhibiting LPS-induced proinflammatory genes expression, cytokines and enzyme release (tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, and inducible nitric oxide synthase), as well as CD86 (M1 marker) expression. In addition to the enhancing effect of antiinflammation, sodium butyrate also promoted PSL-induced M2 macrophages polarization, especially elevated thymus and activation-regulated chemokine (TARC) and arginase-1 (Arg-1) enzyme levels which are involved in tissue repair. Sodium butyrate enhanced antiinflammatory properties and M2-polarization inducing effect of PSLs. Therefore, sodium butyrate may represent a novel approach to enhance PSL-induced macrophage polarization.

Increased plasma miR-24 and miR-191 levels in patients with severe atopic dermatitis: Possible involvement of platelet activation

Platelets are involved in the pathomechanisms of atopic dermatitis (AD). This study aimed to elucidate the levels of platelet-related miRNAs, (miR-24 and miR-191) in the plasma of AD patients and their relationships with the disease severity and laboratory data. miRNAs were detected in the subjects plasma using specifically primed quantitative reverse transcription polymerase chain reaction. The patients with severe AD had significantly higher plasma miR-24 or miR-191 levels than the patients with mild AD, the urticaria patients, and the healthy volunteers. The plasma miR-24 and miR-191 levels of the AD patients were correlated with their serum thymus and activation-regulated chemokine levels. In addition, plasma miR-24 and miR-191 levels were correlated with their plasma levels of platelet factor 4 and β-thromboglobulin. Our findings imply that miR-24 and miR-191 may be involved in the pathomechanisms responsible for the worsening of AD, possibly through their effects on platelet activation.

Serum thymus and activation-regulated chemokine level is associated with the severity of chronic kidney disease-associated pruritus in patients undergoing peritoneal dialysis

Thymus and activation-regulated chemokine (TARC), which induces a Th2-dominated inflammation, is a well-known biomarker that reflects the severity of atopic dermatitis. The present study aimed to evaluate TARC as a Th2-associated marker with chronic kidney disease-associated pruritus (CKD-aP) in patients with peritoneal dialysis (PD). This single-centre cross-sectional study included patients who underwent PD in our hospital between August 2020 and July 2021. The severity and impaired quality of life (QOL) of CKD-aP were assessed using the visual analogue scale (VAS) and Japanese version of the 5-D itch scale (5D-J), respectively. A total of 48 patients with PD were included in the present study. Age and dialysis vintage were (mean ± SD) 64.8 ± 12.0 year and (median (IQR)) 38.5 (11.5-91.5) month, respectively. VAS and 5D-J scores were 3.3 ± 2.0 and 10.5 (9.0-12.0), respectively. Serum TARC level was 481.5 (278.9-603.4) pg/mL (upper limits of normal 450 pg/mL) and significantly correlated with VAS (r = 0.39, p = 0.006) and 5D-J score (r = 0.37, p = 0.009). Multivariate linear analysis revealed that higher serum TARC level was significantly associated with VAS (p < 0.001) and 5D-J score (p < 0.001). Furthermore, the serum brain natriuretic peptide level tended to be associated with VAS (p = 0.060) and 5D-J score (p = 0.029). Serum TARC level is an independent predictor of the severity and impaired QOL of CKD-aP in patients with PD, and TARC might be involved in the pathogenesis of CKD-aP.

Combined prognostic role of TARC and interim 18F-FDG PET/CT in patients with Hodgkin lymphoma-real world observational study.

Although the majority of patients with Hodgkin lymphoma (HL) has recently become long-term survivors, 20%-30% of HL patients have primary refractory disease or relapse. It is essential to identify patients at risk of treatment failure during first-line therapy. To objective of the present study was to investigate the combined prognostic role of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging and thymus and activation-regulated chemokine (TARC) levels in Hodgkin lymphoma. Between 01/01/2013 and 01/03/2019 77 HL patients were enrolled in this study where serum TARC levels were measured by an immunoassay and 18F-FDG PET/CT scans were performed at baseline, after the second cycle of ABVD treatment (interim) and at the end of first-line therapy. Twenty-six patients (34%) had early-stage HL, while 51 patients presented with advanced-stage disease. Fifteen patients had primary refractory HL, while 1 patient relapsed after first-line therapy. Optimal TARC cut-off value for progression-free survival (PFS) was 700pg/mL based on receiver operating characteristic (ROC) curve analysis. With Cox regression analysis, 18F-FDG PET/CT with Deauville scores of 3, 4, or 5 and TARC levels above 700pg/mL predicted treatment failure at interim assessment. Inclusion of HL patients with a Deauville score of 3 to the high-risk population resulted in a 7-fold increase in the estimated risk of relapse compared to patients with Deauville score 4-5 with TARC levels above 700pg/mL. Patients with interim 18F-FDG PET/CT Deauville scores 3-5 had a significant survival benefit if their TARC levels were 700pg/mL. Positive predictive value (PPV) of interim 18F-FDG PET/CT scans with a Deauville score 3-5 was 47.8%, while combined PPV of a similar 18F-FDGPET/CT assessment and elevated TARC levels was 88.8%. Interim 18F-FDG PET/CT and TARC analyzed together accurately identify HL patients who do not respond sufficiently to treatment and who need an early change of therapy.

Serum thymus and activation-regulated chemokine (TARC) levels in newly diagnosed patients with Hodgkin lymphoma: a new promising and predictive tool? Preliminary report

Thymus and activation-regulated chemokine (TARC) is expressed on Reed-Sternberg cells of patients with classical Hodgkin lymphoma (HL) and may serve as a marker in response assessment. In our study, we correlated serum TARC levels with early response to treatment measured by PET/CT in 19 newly diagnosed patients with HL who received ABVD (Adriblastin, Bleomycin, Vinblastine, Dacarbazine) regimen. Finally, 17 patients were analyzed and six of them (35%) achieved PET/CT negativity defined as Deauville (D) 1 or 2 after 2 cycles of ABVD; 11 pts (65%) had D3 on PET/CT. None of the patients presented D 4/5. Median serum TARC levels at diagnosis were significantly higher when compared with healthy controls: 5718 pg/ml vs 76.1 pg/ml (p < 0.001). All study patients were treated with ABVD regimen and there was a significant decrease of baseline serum TARC levels after 2 cycles of therapy. No significant difference of baseline serum TARC levels was demonstrated between patients with D1/2 and D3 whereas levels were significantly decreased after 2 cycles of ABVD in patients D1/2 vs D3; p = 0.049. There was a tendency to higher baseline serum TARC levels in patients with an increased LDH (lactate dehydrogenase) activity (p = 0.08) and in those who progressed when compared with those who maintained response (p = 0.09). Serum TARC levels decrease after chemotherapy and may serve as a marker of response assessment.

Association study of transition of laboratory marker levels and transition of disease activity of atopic dermatitis patients treated with dupilumab.

Dupilumab, a fully human monoclonal antibody that blocks signalling pathways of interleukin (IL)-4 and IL-13, is effective in treating patients with atopic dermatitis (AD). We previously showed that transitions of serum thymus and activation-regulated chemokine (TARC) levels and eosinophil numbers were strongly associated with that of AD activity and that the transitions of serum lactate dehydrogenase (LDH) and immunoglobulin E (IgE) levels were weakly and not associated with that of AD activity, respectively, in patients treated without dupilumab. The purpose of this study was to elucidate whether the association of the transition of laboratory marker levels and transition of disease activity in dupilumab-treated AD patients (present study) was different from that in patients who are not treated with dupilumab (previous study). Sixty AD outpatients treated with dupilumab were included in this study. Associations between the transition of the eczema area and severity index (EASI) score and those of above-mentioned laboratory marker levels were evaluated using a mixed effects model of EASI as the response variable, laboratory markers as fixed effects and patients as random effects. The transitions of serum TARC and LDH levels were associated strongly with that of AD activity, but the transitions of serum IgE level and eosinophil numbers were associated with that of AD activity intermediately and weakly, respectively. Laboratory markers are useful for evaluating the effects of treatments for AD, but the meaning of each laboratory marker depends on the drugs used for treatment.