Serum Thymic Stromal Lymphopoietin Levels Research Articles

Thymic stromal lymphopoietin: evaluating its role as a new marker related to presence of psoriasis vulgaris and its severity

Background Thymic stromal lymphopoietin (TSLP), a proallergic cytokine, and T cell-derived CD40 ligand (CD40L) may collaborate to increase the production of IL-23 in psoriasis patients. One key cytokine, IL-23, is responsible for the unwarranted immune response in psoriasis sufferers. Aim The current study aims to shed light on the possible role of TSLP as a novel biomarker related to presence of psoriasis vulgaris lesions and its severe forms with exclusion of people with atopic dermatitis, allergic rhinitis, rheumatoid arthritis, graft versus host disease (GVHD), blood diseases and patient on anticoagulant therapy as well as pregnant and lactating females. Patients and methods 40 subjects with psoriasis vulgaris participated in the current case-controlled research, whereas 40 healthy volunteers of similar age and gender served as the control group. The degree and extent of the illness were evaluated utilizing the psoriasis area and severity index (PASI) score. Serum was separated after blood samples from the venous blood of the subjects and control participants were taken. As soon as possible, the serum samples were frozen at −20°C. The Sandwich Enzyme-Linked Immunosorbant Assay (ELISA) was utilized to quantify serum TSLP. Results The case group’s serum TSLP levels rose statistically substantially more than those of the control group. In the cases group, there was a statistically strong positive relation between serum TSLP levels and PASI scores (P: < 0.001). There is a statistically strong positive relation between serum TSLP and patients’ age and illness duration, a statistically substantial rise in blood TSLP values in psoriatic arthritis patients and smokers. Conclusion Patients with psoriasis have higher serum TSLP levels, which are proportional to the disease’s severity.

Peripheral Multiple Cytokine Profiles Identified CD39 as a Novel Biomarker for Diagnosis and Reflecting Disease Severity in Allergic Rhinitis Patients.

Allergic rhinitis (AR) is a common clinical problem, and immune cells and cytokines were proven to be pivotal in its pathogenesis. Our aim is to measure the peripheral concentrations of multiple cytokines in AR patients and identify novel biomarkers for diagnosis and disease severity. Peripheral blood samples were collected from 50 AR patients, including 25 mild AR (MAR) patients and 25 moderate-severe AR patients (MSAR), and 22 healthy controls (HCs), and multiple cytokine profiling was outlined by Luminex assay. Cytokine levels were compared among the three groups, and their correlations with disease severity were evaluated. The candidate cytokines were further verified by enzyme-linked immunosorbent assay (ELISA) in a validation cohort. Multiple cytokine profiling revealed that CD39 and interferon (IFN)-γ levels were reduced, and interleukin (IL)-13, IL-5, IL-33, and thymic stromal lymphopoietin (TSLP) levels were elevated in the AR group than the HC group (P < 0.05). Receiver operating characteristic (ROC) curves presented that serum CD39 and IL-33 exhibited strong diagnostic abilities, and serum CD39 and IL-10 presented capacities in distinguishing disease severity (AUC > 0.8, P < 0.05). Moreover, CD39 concentrations were decreased, and IL-10, IL-5, and TSLP concentrations were enhanced in the MSAR group more than in the MAR group. Correlation analysis results showed that serum CD39, IL-5, and TSLP levels were associated with total nasal symptom score (TNSS) and visual analogue score (VAS) (P < 0.05). Further data in the validation cohort suggested that serum CD39 levels were reduced, and IL-5 and TSLP levels were increased in AR patients, especially in MSAR patients (P < 0.05). ROC results revealed potential values of serum CD39 in diagnosis and disease severity evaluation in AR patients (P < 0.05). This study highlighted that peripheral multiple cytokine profiles were significantly varied in AR patients and associated with disease severity. The results in discover-validation cohorts implied that serum CD39 might serve as a novel biomarker for diagnosing AR and reflecting its disease severity.

Dependence of thymic stromal lymphopoietin serum concentration from bronchial asthma control level and lung function results in patients of different age groups

Introduction. Bronchial asthma (BA) pathogenesis is settled by bronchial wall inflammation, which is the main treatment target.Aim. To study the dependence of thymic stromal lymphopoietin (TSLP) concentration in serum and nasal brush-biopsies from age, spirometry data deterioration and blood eosinophils in patients with uncontrolled BA.Materials and methods. Patients with uncontrolled BA of three age groups: children (6–11 y.o., n = 38), adolescents (14–17 y.o., n = 35) and adults (25–50 y.o., n = 31) were included in 1-year long open prospective study. Clinical history, АСТ/сАСТ questionnaires, lung function test (LFT), common blood count, serum and nasal material to evaluate TSLP were obtained during first visit, if there were no any signs of acute respiratory infection for not less than 14 days. Maintenance therapy was revised based on firstvisit findings. Patient were consequently examined twice with 6 months intervals, examination data, LFT readings, ACT results and eosinophil counts were collected. Statistical analyses included ANOVA (Kruskal-Wallis test) and Pearson’s correlation (r). Differences accepted significant with р &lt; 0,05.Results. Serum TSLP levels did not differ between age groups. TSLP concentration correlate directly and significantly with duration of uncontrolled BA in previous 12 months (r = 0.74). In patients with atopic BA, maximum TSLP level was in dust mites sensitized group (792.6 ± 114.1 pg/ml). We have found greater serum TSLP concentration in patients who demonstrated FEV1 below normal even on optimal controller therapy at Visit 3. Eosinophil count randomly changed inside normal values and did not correlate with asthma control or TSLP level.Conclusion. Prognosis of future asthma exacerbations and LFT decrease is less favourable in patients with high serum TSLP level.

Effect of halometasone cream combined with Simiao pill on the therapeutic effect and expression of serum leukotriene B4 (LTB4) and thymic stromal lymphopoietin (TSLP) in patients with eczema, and the factors influencing its clinical efficacy.

Chronic eczema has the characteristics of a long treatment cycle and repeated attacks, which seriously affects the daily life and work of patients. Topical glucocorticoids are the first-line treatment for chronic eczema. This study aimed to retrospectively analyze the effects of halometasone cream combined with Simiao pill on the efficacy and expression of serum leukotriene B4 (LTB4) and thymic stromal lymphopoietin (TSLP) in patients with eczema, and identify the factors influencing its clinical efficacy. We retrospectively collected the medical records of 195 patients with chronic eczema treated in the dermatology department from January 2020 to May 2021, and divided them into two groups according to medication: 98 cases were treated with halometasone cream (control group) and 97 cases were treated with halometasone ointment combined with Simiao pill (observation group). The severity of eczema, quality of life, clinical efficacy, LTB4 and TSLP levels, and safety were compared between the two groups. Multivariate logistic regression analysis was used to determine the independent factors affecting clinical efficacy. After treatment, the Eczema area and severity index (EASI) and Dermatology Life Quality Index (DLQI) scores in the observation group were markedly lower than those of the control group (P<0.05). The total clinical effective rate of the observation group was 88.8%, which was notably higher than that of the control group 70.1% (P=0.001). The concentrations of serum LTB4 and TSLP in the observation group were markedly lower than those in the control group (P<0.05). Logistic regression analysis showed that the treatment regimen, digestive system symptoms, heavy aching limbs, and damp-heat tongue and pulse were independent factors affecting the curative effect of the patients (P<0.05). Simiao pill combined with halometasone cream can effectively improve chronic eczema and enhance the clinical efficacy of treatment, which may be related to the reduction of serum LTB4 and TSLP levels. The treatment plan, digestive system symptoms, heavy aching limbs, and damp-heat tongue and pulse are the main factors that affecting the clinical curative effect. Thus, clinical intervention programs should be made according to the above factors to improve the quality of life of patients.

Serum Levels of Epithelial-Derived Cytokines as Interleukin-25 and Thymic Stromal Lymphopoietin after a Single Dose of Mepolizumab in Patients with Severe Non-Allergic Eosinophilic Asthma: A Short Report.

The bronchial epithelium has continuous contact with environmental agents initiating and maintaining airway type 2 inflammation in asthma. However, there is a lack of data on whether reduced airway eosinophilic inflammation can affect the production of epithelial-derived mediators, such as interleukin-25 (IL-25) and thymic stromal lymphopoietin (TSLP). The aim of this study was to investigate the changes in serum levels of IL-25 and TSLP after a single dose of mepolizumab, a humanized monoclonal antibody to interleukin-5 (IL-5), in patients with severe non-allergic eosinophilic asthma (SNEA). We examined 9 SNEA patients before and four weeks after administration of 100 mg mepolizumab subcutaneously. The fractional exhaled nitric oxide (FeNO) level was analysed using an electrochemical assay (NIOX VERO®, Circassia, UK). Serum IL-25 and TSLP levels were measured by ELISA. Four weeks after the single dose of mepolizumab, blood eosinophil count significantly decreased from 0.55 ± 0.20 × 109/l to 0.14 ± 0.04 × 109/l (p = 0.01) and FEV1 increased from 2.1 ± 0.5 l (65.4 ± 8.8% of predicted) to 2.6 ± 0.4 l (76.4 ± 9.1% of predicted) (p = 0.04), while FeNO level has not changed (32.3 ± 8.4 vs 42.9 ± 12.6 ppb). Serum IL-25 level significantly decreased from 48.0 ± 17.2 pg/mL to 34.8 ± 17.1 pg/mL (p = 0.02) with same tendency in TSLP level: from 359.8 ± 71.3 pg/mL to 275.6 ± 47.8 pg/mL (p = 0.02). It has also been noticed a significant relation between changes in the blood eosinophil count and serum IL-25 level (r = 0.81, p = 0.008), as well as between changes in serum IL-25 and TSLP levels (r = 0.93, p = 0.004) after a single dose of mepolizumab. Thus, anti-IL-5 treatment with mepolizumab might diminish the production of bronchial epithelial-derived cytokines IL-25 and TSLP in patients with SNEA which is potentially related to reduced eosinophilic inflammation. This trial is registered in ClinicalTrial.gov with identifier NCT03388359.

Serum TSLP is a potential biomarker of psoriasis vulgaris activity.

BackgroundThe proallergic cytokine, thymic stromal lymphopoietin (TSLP) may synergize with T cell–derived CD40 ligand (CD40L) to allow IL-23 production in patients with psoriasis. IL-23 is a central cytokine that mediates the inappropriate immune reaction in patients with psoriasis.ObjectiveThe aim of the study was to correlate serum level of TSLP with psoriasis severity.MethodsThe study was carried out on 53 patients with psoriasis. They were divided into mild, moderate, and severe according to PASI score. The patients’ ages ranged from 10 to 62 years. The patients included 29 males and 24 females. A total of 53 healthy subjects with matched age and sex served as control group. Blood samples were collected from the venous blood of the patients and control subjects then the serum was separated. The serum samples were immediately frozen at -20°C. Serum TSLP was measured by Sandwich Enzyme–linked Immunosorbant Assay (ELISA).ResultsThere was a statistically very highly significant increase (p<0.001) in serum TSLP levels among the case group (1042.7±812.93) compared to the control group (314.21±220.78). There was also a statistically very highly significant increase (p<0.001) in serum TSLP levels with increased psoriasis severity estimated by PASI score.ConclusionIn this study, we found that serum TSLP is elevated in psoriasis patients and is correlated with disease severity.

Thymic stromal lymphopoietin levels are increased in patients with celiac disease.

Thymic stromal lymphopoietin (TSLP) is a cytokine produced by epithelial cells in the lungs, skin, and intestinal mucosa and is involved in several physiological and pathological processes. In this study, we evaluated serum TSLP levels in patients with celiac disease (CD). The prospective study was conducted at a gastroenterology outpatient clinic between March 2018 and August 2018. Eighty-nine participants aged between 18 and 75 years were classified into following groups: 22 patients with newly diagnosed CD; 20 patients with CD who were compliant with a gluten-free diet (GFD); 32 patients with CD who were not compliant with a GFD; and 15 healthy controls. Demographic characteristics, disease duration, and selected biochemical and hematologic parameters were recorded and compared between groups. Median serum TSLP levels were 1193.65 pg/mL (range: 480.1-1547.1) in newly diagnosed CD patients, 110.25 pg/mL (range: 60.3-216.7) in CD patients who were compliant with a GFD, 113.1 pg/mL (range: 76.3-303.4) in CD patients who were not compliant with a GFD, and 57 pg/mL (range: 49-67.8) in healthy controls. Overall, there was a significant difference in serum TSLP levels between groups (p = 0.001). Patients with newly diagnosed CD had the highest serum TSLP levels. There was no significant difference in serum TSLP levels between patients with CD who were and were not compliant with a GFD. TSLP appears to be involved in the pathogenesis of CD. Further studies are required to determine if the TSLP signaling pathway can be used in the treatment of CD.

Tripterygium Wilfordii inhibits tonsillar IgA production by downregulating IgA class switching in IgA nephropathy.

IgA nephropathy (IgAN) is characterized by high serum IgA levels and IgA deposition in the renal mesangium. Recent research has indicated that pathogenic IgA may originate from affected tonsils, where present enhancement of IgA production by IgA class switching and immuno-activation. Tripterygium Wilfordii (TW) was found to be especially effective in IgAN by its’ immunosuppression effect. Given this background, we investigated the mechanisms underlying the role of TW in the generation of IgA and IgA class switching in tonsillar GCs of IgAN patients. Immunohistochemistry and RT-PCR revealed that the expression of thymic stromal lymphopoietin (TSLP) and IgA inducing cytokines were decreased in the tonsils of IgAN patients with TW treatment compared with those without treatment, followed by significantly decreased of IgA-bearing cells. The location of TSLP and IgA inducing cytokines in tonsillar tissue was confirmed by double immunofluorescence. Importantly, TW inhibit TSLP and IgA production in isolated FDC-associated clusters. Serum TSLP levels were decreased and correlated with IgA downregulation in the tonsils and serum of IgAN patients. These data indicated that TW may be involved in IgA production in the tonsils of IgAN patients, inhibiting IgA class switching in IgAN patients through the cooperative roles of AID, TGF-β1, BAFF, and APRIL, highlighting a promising strategy for therapeutic intervention in IgAN.

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.

Abstract 727: TSLP expression and high serum TSLP level indicate a poor prognosis in gastric cancer patients

Abstract Purpose: Thymic stromal lymphopoietin (TSLP) plays an important role in promoting tumor survival, by manipulating the immune response and angiogenesis. However, the clinical significance of TSLP in gastric cancer is unclear. Method: Immunohistochemistry was used to investigate TSLP expression in non-cancerous gastric mucosa and gastric cancer tissue from patients with gastric cancer. Serum TSLP levels were measured using an enzyme-linked immunosorbent assay. Results: Tumors with TSLP expression were significantly larger than those without TSLP expression. TSLP expression was observed more frequently in advanced (T2/T3/T4) than in early (T1) gastric cancer and in stage 3/4 than in stage 1/2. Lymph node metastasis, liver metastasis, positive peritoneal lavage cytology, lymphatic invasion, and vascular invasion occurred significantly more often in TSLP-expressing than in non-expressing tumors. The prognosis of patients with TSLP-positive tumors was significantly worse than that of patients with TSLP-negative tumors. Patients with high serum TSLP concentrations also had a significantly worse prognosis than those with low concentrations. Multivariate analysis identified serum TSLP level as an independent prognostic indicator. Conclusion: TSLP is closely related to the progression of gastric cancer and may predict survival in these patients. Citation Format: Joji Watanabe, Hiroaki Saito, Kozo Miyatani, Masahide Ikeguchi, Yoshihisa Umekita, Shinji Otani, Shunichi Tsujitani. TSLP expression and high serum TSLP level indicate a poor prognosis in gastric cancer patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 727.

Elevated Serum Levels of Thymic Stromal Lymphopoietin in Wheezing Children Infected with Human Metapneumovirus.

Our aim was to study the epidemiology and clinical manifestations of human metapneumovirus (hMPV) infection in children in the Suzhou area, China, and to investigate the effect of thymic stromal lymphopoietin (TSLP) on wheezing in hMPV-infected children. The study included 13,533 children with respiratory tract infections who were admitted to the Children's Hospital of Soochow University between January 2009 and December 2014. Clinical data were recorded. Plasma levels of TSLP, interleukin (IL)-4, and IL-2 were compared among 35 wheezing children with single hMPV infection, 15 non-wheezing children with hMPV infection, and 35 wheezing children with other viral infections. The annual rates of hMPV infection from 2009 to 2014 were 2.33%, 6.41%, 3.29%, 3.52%, 0.23%, and 0.64%, respectively, peaking in 2010. The number of CD3-/CD16+/CD56+ cells was significantly lower in inpatients with hMPV infection than that in patients with other viral infections. Serum levels of TSLP and IL-4 in wheezing children with hMPV infection were significantly higher than the levels in the other 2 groups. hMPV is a common viral pathogen that causes respiratory infections in children in Suzhou, but annual rates have declined since 2010. Infection with hMPV may affect cell-mediated immunity. Serum TSLP levels were elevated after hMPV infection.

TSLP, IL-31, IL-33 and sST2 are new biomarkers in endophenotypic profiling of adult and childhood atopic dermatitis.

Recent years have seen growing interest in identifying new biomarkers in atopic dermatitis (AD) that could serve as indicators of disease severity and predictors of treatment response. We compared serum levels of thymic stromal lymphopoietin (TSLP), interleukin(IL)-31, IL-33 and soluble(s)ST2 in AD patients and healthy controls, investigated the possible correlation with disease severity, investigated if other atopic comorbidities could play a role, and assessed their potential as biomarkers in AD. Using standard enzyme-linked immunosorbent assay techniques, we measured target serum levels in 71 adults and 61 children with AD, and 31 adult controls. We characterized our cohort by disease severity, radioallergosorbent test status concerning both dietary and inhalant allergens, and anamnestic reports of food allergy, concomitant allergic asthma and/or allergic rhinitis. Serum levels of TSLP, IL-31 and IL-33, but not sST2, were significantly elevated in AD patients compared with controls. In AD patients, both IL-31 and IL-33 serum levels were higher in children than in adults, while the opposite was the case for sST2. We observed no correlation between disease severity and any of the investigated targets. While serum TSLP levels were unaffected by concomitant allergies and atopic comorbidities, serum levels of IL-31, IL-33 and sST2 were affected to a small extent. We found a positive correlation between TSLP, IL-31 and IL-33, and an inverse relationship between IL-33 and sST2. The studied targets hold little potential as indicators of disease severity. The serum values of our targets show robustness against atopic comorbidities, allergies and changes in disease severity. This robustness strengthens their potential use in biomarker-based stratification and could be instrumental in identifying subgroups and predicting the possible benefit of therapeutic and prevention approaches.

Thymic stromal lymphopoietin in tonsillar follicular dendritic cells correlates with elevated serum immunoglobulin A titer by promoting tonsillar immunoglobulin A class switching in immunoglobulin A nephropathy

Immunoglobulin A (IgA) nephropathy (IgAN) is characterized by high serum IgA levels and IgA deposition in the renal mesangium. Previous studies suggest that elevated serum IgA partly originates from the tonsils. Here, we investigated the mechanisms of IgA production in the tonsils of patients with IgAN. Immunohistochemistry revealed that the number and relative percentage of IgA-bearing cells were significantly increased in the tonsils of IgAN patients. Compared with non-IgAN patients, enhanced IgA class switching and overexpression of thymic stromal lymphopoietin (TSLP), TSLP receptor (TSLPR), activation-induced cytidine deaminase (AID), transforming growth factor-β1 (TGF-β1), Bcell-activating factor of the tumor necrosis factor family (BAFF), and a proliferation-inducing ligand (APRIL) were detected in follicular dendritic cells (FDCs) of tonsillar germinal centers from IgAN patients. Importantly, TSLP correlated with IgA production in isolated FDC-associated clusters. Serum TSLP levels were increased and correlated with IgA overexpression in the tonsils and serum of IgAN patients. These data indicated that TSLP overexpression in tonsillar FDCs may promote IgA class switching in IgAN patients through the cooperative roles of AID, TGF-β1, BAFF, and APRIL. Therefore, interactions between TSLP in FDCs and IgA production in tonsils may be an important mechanism contributing to the pathogenesis of IgAN.

The Notch Intracellular Domain Has an RBPj-Independent Role during Mouse Hair Follicular Development

Ligand-dependent activation, γ-secretase-processed cleavage, and recombining binding protein Jk (RBPj)-mediated downstream transcriptional activities of Notch receptors constitute the "canonical" Notch signaling pathway, which is essential for skin organogenesis. However, in Msx2-Cre mice, keratinocyte-specific deletion of the Rbpj gene in utero produced a significantly milder phenotype than either global Notch or γ-secretase loss. Herein, we investigated the underlying mechanisms for this apparent noncanonical signal using mouse genetics. We found no evidence that ligand back-signaling contributed to skin organogenesis. The perdurance of RBPj protein did not establish an epigenetic memory of a canonical signal in the youngest epidermal stemcells, and Notch targets were not derepressed. We provide evidence that γ-secretase-dependent but RBPj-independent Notch intracellular domain activity operating in the first hair follicles is responsible for a delay in follicular destruction, which results in lower serum thymic stromal lymphopoietin levels, milder B-cell lymphoproliferative disease, and improved survival in Msx2-Cre(+/tg);Rbpj(f/f) mice. Minimal amounts of the Notch intracellular domain were sufficient for rescue, which was not mediated by transcription, suggesting that the Notch intracellular domain is acting through a novel mechanism.

Atopic dermatitis phenotype with early onset and high serum IL-13 is linked to the new development of bronchial hyperresponsiveness in school children.

Atopic dermatitis (AD) is characterized by a heterogeneous clinical spectrum, and some forms of AD are associated with the initial steps of allergic march. The aims of this study were to determine AD phenotypes in school-age children and investigate their associations with the allergic march in each cluster. We included 242 children (6-8 years) with current AD from the Children's HEalth and Environmental Research study, a 4-year prospective follow-up study with 2-year survey intervals. Latent class analysis was used. Serum IL-13 and thymic stromal lymphopoietin (TSLP) levels at the time of enrollment were measured using ELISA. We identified four current AD phenotypes in children, characterized as 'early onset with low atopy' (26.4% of the sample; group 1), 'early onset with high atopy and high eosinophil percentages' (48.3%; group 2), 'late onset with low atopy' (9.9%; group 3), and 'late onset with high atopy and normal eosinophils' (15.3%; group 4). Although groups 2 and 4 demonstrated high atopic burden, children in group 2 showed the persistence of AD and eosinophilia associated with a high prevalence of new cases of bronchial hyper-responsiveness and asthma symptoms during follow-up. The serum IL-13 level was significantly increased in the early-onset AD groups, but there was no significant difference in the serum TSLP levels across all four groups. An allergic march-associated AD phenotype exists that is characterized by early onset of AD with its persistence, increased serum IL-13 levels, high atopy, and a persistently increased blood eosinophil percentage.

Investigation of Skin Barrier Functions and Allergic Sensitization in Patients with Hyper-IgE Syndrome.

Hyper-IgE syndrome (HIES) is a severe primary immunodeficiency, characterized by increased serum IgE levels as well as recurrent infections and atopic dermatitis (AD)-like skin lesions. AD is a chronic inflammatory skin disease with immunologic alterations (Th2-Th22 polarization) and characteristic skin barrier dysfunctions. Our aim was to investigate physicochemical skin barrier alterations and allergic sensitization in STAT3-HIES patients in order to explore whether skin barrier dysfunction can play a role in the eczematoid skin lesions in these patients. In our experiments STAT3 and FLG mutation analyses were performed in STAT3-HIES (n = 7) and AD (n = 49) patients. Laboratory parameters (LDH and Eos counts), immunologic alterations (Th17 cell counts), allergic sensitization (total and specific IgE levels, skin prick tests, and medical history records), skin barrier changes [transepidermal water loss (TEWL), skin pH], serum and stratum corneum thymic stromal lymphopoietin (TSLP) levels were also examined. Impaired Th17 cell numbers, but normal physicochemical barrier functions, as well as serum and stratum corneum TSLP levels, were found in STAT3-HIES, while these parameters were significantly altered in AD patients. Allergic sensitization was detected in nearly all AD patients, while no signs of sensitization occurred in STAT3-HIES. Our study demonstrated that the skin barrier functions of STAT3-HIES patients are not damaged and they differ significantly from the altered skin barrier functions of AD patients. A well-functioning physicochemical skin barrier may be one of the explanations on the contradiction between the extremely high total IgE levels and the lack of allergic sensitization in these patients. Our study underlines the importance of skin barrier in the development of allergic sensitization.

Increased serum thymic stromal lymphopoietin in children with atopic dermatitis

The present study investigated the relationship between serum thymic stromal lymphopoietin (TSLP) levels and the presence and severity of atopic dermatitis (AD). Serum TSLP levels, blood eosinophil counts, and serum total and specific immunoglobulin E (IgE) levels were measured in 232 children. Subjects were characterized as having atopic eczema (AE; n=75), non-atopic eczema (NAE; n=70), or normal controls (n=87). Serum TSLP levels in children with AD were significantly higher than normal controls but there were no differences in children with atopic and non-atopic eczema. However, serum TSLP levels in children with AD were not significantly correlated with disease severity, blood eosinophil counts and serum total IgE levels. Our findings show an association between TSLP and AD including both AE and NAE. It is suggested that TSLP may play a contributory role in the pathogenesis of AD regardless of the presence of atopy.

Skin-Derived TSLP Triggers Progression from Epidermal-Barrier Defects to Asthma

Author SummaryEczema (atopic dermatitis) is a common allergic skin inflammation that has a particularly high prevalence among children. Importantly, a large proportion of people suffering from eczema go on to develop asthma later in life. Although the susceptibility of eczema patients to asthma is well documented, the mechanism that mediates “atopic march”—the progression from eczema to asthma—is unclear. We used genetic engineering to generate mice with chronic skin-barrier defects and a subsequent eczema-like disorder. With these mice, we were able to investigate how skin-specific defects predisposed the lungs to allergic asthma. We identified thymic stromal lymphopoietin (TSLP), a cytokine that is secreted by barrier-defective skin into the systemic circulation, as the agent sensitizing the lung to allergens. We demonstrated that high systemic levels of skin-derived TSLP were both required and sufficient to render lung airways hypersensitive to allergens. Thus, these data suggest that early treatment of skin-barrier defects to prevent TSLP overexpression, and systemic inhibition of TSLP, may be crucial in preventing the progression from eczema to asthma.

Increased serum thymic stromal lymphopoietin levels in patients with cutaneous T cell lymphoma

Increased serum thymic stromal lymphopoietin levels in patients with cutaneous T cell lymphoma

Serum thymic stromal lymphopoietin levels are not elevated in patients with atopic dermatitis

Serum thymic stromal lymphopoietin levels are not elevated in patients with atopic dermatitis