Atopic Subjects Research Articles

Urinary eosinophil-derived neurotoxin is associated with reduced lung function in pediatric asthma.

Eosinophil-derived neurotoxin (EDN) is a biomarker for eosinophilic activation. Urinary (u) EDN may allow non-invasive monitoring of asthma, but clinical recommendations are lacking. We assessed the potential of uEDN as a marker of disease activity in pediatric asthma. We assessed urine samples of 371 children from the German ALLIANCE study cohort, from which we had: 169 preschool wheezers (<6 years), 80 asthmatics (≥6 years), and 122 healthy controls using the ImmunoCAP™ EDN Assay. Creatinine (Cr)-adjusted uEDN values were analyzed using correlations, association tests, (non) parametric statistics, multiple linear, and multivariable regression. uEDN/uCr values were higher in atopic versus non-atopic preschool-aged subjects (p = .035) and associated with the sum of allergen-specific IgE in younger (r = 0.24, p = .003), and older subjects (r = 0.23, p = .043). uEDN/uCr was marginally a good determinant for atopy (p = .078, for subjects aged <6 years, and p = .058 for subjects ≥6 years). Children with the T2-high phenotype had higher uEDN/uCr (p < .001) versus T2-low-irrespective of using uEDN/uCr or blood eosinophils in combination to allergen sIgE for disease phenotyping. uEDN/uCr significantly correlated with reduced lung function among asthmatics (FEV1 z-scores: r = -0.30, p = .007, and FEV1/FVC z-scores: r = -0.24, p = .038). Using multivariable modeling, uEDN/uCr was an independent determinant of FEV1 (p = .038), and to a lesser extent, FEV1/FVC (p = .080). uEDN/uCr may serve as a non-invasive biomarker for clinical features such as lung function in pediatric asthma. We highlight the utility of uEDN/uCr as a biomarker that can be easily assessed using widely available robust diagnostic immunoassays.

Distinct Adverse Reactions to mRNA, Inactivated Virus, and Adenovirus Vector COVID-19 Vaccines: Insights from a Cohort Study on Atopic and Non-Atopic Subjects in Brazil.

The emergence of COVID-19 caused by SARS-CoV-2 prompted an unprecedented global response to develop vaccines at an accelerated pace. Messenger RNA (mRNA) and adenovirus vector vaccines emerged as the frontrunners in global immunization efforts, significantly reducing hospitalization, severity, and mortality, supplemented by inactivated virus-based vaccines in developing countries. However, concerns regarding adverse effects, including allergic reactions, have been raised. This study aimed to investigate the adverse effects following COVID-19 vaccination, particularly in atopic and non-atopic individuals. A cohort of 305 volunteers receiving BNT162, ChAdOx1, or CoronaVac vaccines were assessed based on a Skin Prick Test (SPT), specific IgE levels, and clinical history of asthma and rhinitis. Adverse effects were self-reported and scored across the different vaccination shots. The results indicated a notable presence of mild adverse effects following the first and third doses, regardless of vaccine type. ChAdOx1 recipients experienced more adverse effects compared to those receiving BNT162 and CoronaVac, including headaches, muscle pain, fever, chills, nausea, and flu-like symptoms. Atopic individuals receiving ChAdOx1 reported more adverse effects, such as muscle pain, fever, and chills, compared to non-atopic individuals. Conversely, headaches were more frequently reported in non-atopic individuals receiving BNT162 compared to atopic individuals. No anaphylaxis or allergic reactions were reported, indicating valuable evidence supporting the safety of COVID-19 vaccination in individuals with respiratory allergies. This study highlights the importance of understanding vaccine-related adverse effects, particularly in vulnerable populations, to inform vaccination strategies and address safety concerns in global immunization campaigns.

Analysis of suspected adverse reactions to food supplements containing beehive products: an update from the Italian Phytovigilance System.

Beehive products are widely used in food supplements; however, their composition variability and allergenic components have raised some concerns. This work aims to provide information about the beehive products safety profile by evaluating the suspected adverse reactions (ARs). The suspected report of ARs collected within the Italian Phytovigilance System (IPS) were evaluated. The clinical and demographic characteristics of the cases were described, and the causality assessment performed. 61 reports were analysed, mainly concerned women. Serious events were reported in 17 forms (28%). The ARs (n=116) referred to respiratory (25.0%), skin (24.1%), and gastrointestinal disorders (21.5%). Label warnings for atopic subjects were present only in 7 food supplements. The causality assessment was mostly probable (54.1%). Present findings outline relevant information about the safety issues of beehive product consumption, especially in atopic or allergic subjects, and strengthen the importance of IPS to point out safety signals.

Correlation of Blomia tropicalis-specific immunoglobulin epsilon profiles with family history of atopy in a Filipino population.

House dust mites are the major source of indoor allergens in the tropical and subtropical regions with Blomia tropicalis (Bt) allergens as one of the leading causative agents of sensitization among patients from the tropics. Despite the clinical importance of Bt in various populations, its allergenicity remains unclear among Filipino allergic patients. This study determined the sensitization profiles of allergic Filipinos against Bt allergens and its correlation with atopy. Total immunoglobulin epsilon (IgE) (n = 960), Bt-specific IgE (n = 247), and Blomia tropicalis 5 (Blo t 5)-specific IgE (n = 87) profiles of allergic and nonallergic subjects were measured through enzyme-linked immunosorbent assay (ELISA). Point-biserial correlation coefficient was used to determine the association between Bt-specific IgE levels and selected demographics. Inhibition ELISA was performed to measure the inhibition capacity of recombinant Blo t 5 (rBlo t 5) against Bt allergen extracts. Mean total IgE levels of allergic cases (n = 171) were significantly higher (P < 0.001) compared to the mean IgE levels of nonallergic controls (n = 76). Among allergic subjects, 58% were sensitized to Blo t extract and 80% of which were sensitized to rBlo t 5 allergen. A positive correlation was observed between Bt-specific IgE and family history of atopic disease (P = 0.031). Inhibition assay revealed that 54% mean reactivity of 7 plasma samples was caused by rBlo t 5, validating that rBlo t 5 is a major allergen in Bt. This study has shown the importance of Bt as an allergen source that sensitizes atopic Filipino subjects. Hence, inclusion of Bt allergen extract and rBlo t 5 in the panel for allergy diagnosis and immunotherapy in Filipino populations is strongly recommended.

Comment on 'Dupilumab significantly improves sleep in adults with atopic dermatitis: results from the 12-week placebo-controlled period of the 24-week phase IV randomized double-blinded placebo-controlled DUPISTAD study'.

In this letter to the editor, we respond to the article by Merola et al. titled ‘Dupilumab significantly improves sleep in adults with atopic dermatitis: results from the 12-week placebo-controlled period of the 24-week phase IV randomized double-blinded placebo-controlled DUPISTAD study’. We add to the authors’ discussion on the discrepancy between objective and subjective measures of sleep in people with atopic dermatitis treated with dupilumab.

Phosphorylated p38 MAP kinase expression by leucocytes is increased in allergic humans and associated with IgE responses.

Mitogen-activated protein kinases (MAPK) activate cascades that regulate cell proliferation, differentiation and death. Phosphorylated (phos-)p38 MAPK is a cell-signalling pathway associated with Th2 cytokine responses, which is required for immunoglobulin (Ig)E production. It is unknown whether MAPK are associated with IgE production. We examine the evidence linking p38 MAPK to inflammatory responses. Phos-p38, extracellular signal-related kinase (ERK) and c-JUN-n terminal (JNK) MAPK expression by blood leucocyte subsets and levels of serum Igs were measured in blood from adults with asthma and/or rhinoconjunctivitis (N = 28) and non-asthma (N = 10) (flow cytometry, microfluorenzymeimmunoassay). Peripheral blood mononuclear cells (PBMC) from allergic subjects were cultured for 10 days ± anti-CD40/recombinant IL-4 ± inhibitor of phos-P38. Culture supernatants were assayed for IgE (ELISA). Phos-p38 MAPK expression by all leucocyte subsets of allergic subjects was associated with serum IgE levels (p ≤ 0.01), after adjusting for cell counts, age, sex, race and smoking status (p ≤ 0.04). Leucocyte expression of phos-ERK and JNK did not correlate with IgE (p = 0.09-0.99). Instead, phos-ERK expression was associated with serum IgG. When PBMC from atopic subjects were cultured for 10 days with anti-CD40/rhIL-4, IgE levels were 26.2 ± 18 ng/mL. Inclusion of SB202190 (5-20 μg/mL), a specific inhibitor of phos-p38 MAPK, in culture suppressed IgE production in dose-dependent manner, with peak suppression obtained with SB202190 at 20 μg/mL (82.1% ± 11.8) (p = 0.0001), with virtually no cytotoxicity (<5%). Different MAPK pathways may be associated with IgE (p38) and IgG (ERK) responses. Phos-p38 MAPK can be a potential anti-allergy drug target.

Safety, Pharmacokinetics and Preliminary Efficacy of IL4-Rα Monoclonal Antibody AK120 in Both Healthy and Atopic Dermatitis Subjects: A Phase I, Randomized, Two-Part, Double-Blind, Placebo-Controlled, Dose-Escalation, First-In-Human Clinical Study.

Interleukin-4 (IL-4) and interleukin-13 (IL-13) are two essential cytokines involved in the T helper 2 (Th2)-mediated inflammatory response to diseases, such as atopic dermatitis (AD). AK120 is a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody (mAb) directed against the IL-4 receptor alpha (IL-4Rα) subunit shared by the IL-4 and IL-13 receptor complexes. This mAb inhibits the signaling of the IL-4 and IL-13 cytokines. The study consisted of two parts. Part 1 was a single ascending dose (SAD) study with five cohorts (receiving 15, 50, 150, 300 or 600mg of AK120, respectively) of healthy subjects; part 2 was a multiple ascending dose (MAD) study with four cohorts (receiving AK120 at doses of 300mg once every 2 weeks [Q2W], 300mg once weekly [QW], 150 mg QW or 75mg QW) of subjects with AD. A total of 81 subjects (40 in part 1, 41 in part 2) were enrolled in the study. The compound was safe and well tolerated in both a SAD up to 600mg in healthy subjects and in a MAD from 75 to 600mg in subjects with AD. The exposure of AK120 increased in an approximately dose-dependent manner upon subcutaneous dosing. The levels of the biomarkers serum thymus and activation-regulated chemokine ligand 17 (TARC/CCL17) and immunoglobulinE decreased from baseline after AK120 administration, indicating the inhibitionoftheIL-4/IL-13 signaling pathways. AK120 showed improved Eczema Area and Severity Index (EASI) scores, and the proportion of subjects with Investigator Global Assessment (IGA) score 0/1 increased after AK120 treatment. AK120 exhibited an acceptable safety profile in healthy and AD subjects, and showed preliminary efficacy. These findings support the continued investigation of AK120 for treating AD. ClinicalTrials.gov identification number: NCT04256174.

Sputum Neurturin Levels in Adult Asthmatic Subjects.

Neurturin (NRTN) is a neurotrophic factor that was originally identified in the development and maintenance of neural cells. Recent studies involving NRTN knockout mice have reported its anti-inflammatory effects in allergic airway conditions. However, the role of NRTN in human asthma has not yet been identified. The purposes of the present study were to confirm the presence of NRTN in the airways and to investigate the clinical and pathogenetic roles of NRTN in asthma. The NRTN levels in the induced sputum were measured by enzyme-linked immunosorbent assay (ELISA). Relationships between NRTN and clinical characteristics, asthma control status, and airway inflammation were assessed. Sixty-four asthmatic subjects were enrolled in the study. All asthmatic subjects had detectable sputum NRTN levels, with a mean (SD) level of 2.03 (1.29) ng/mL. The sputum NRTN levels had significant positive correlations with sputum eosinophil and exhaled nitric oxide levels and were significantly higher in the atopic subjects than in the non-atopic subjects. No significant difference in sputum NRTN levels were observed for asthma control status and asthma exacerbation. In sputum inflammatory analyses, sputum NRTN level was positively correlated with interleukin (IL)-5 and IL-13 levels, and negatively correlated with matrix metalloproteinase (MMP)-9 level. It is plausible that sputum NRTN could serve as a new marker for Type 2 airway inflammation, implicating its role in the process of airway remodeling in asthma. Future studies should investigate the clinical relevance of sputum NRTN level in prospective analyses.

Rapid reduction in Staphylococcus aureus in atopic dermatitis subjects following dupilumab treatment

Atopic dermatitis (AD) is an inflammatory disorder characterized by dominant type 2 inflammation leading to chronic pruritic skin lesions, allergic comorbidities, and Staphylococcus aureus skin colonization and infections. S aureus is thought to play a role in AD severity. This study characterized the changes in the host-microbial interface in subjects with AD following type 2 blockade with dupilumab. Participants (n= 71) with moderate-severe AD were enrolled in a randomized (dupilumab vs placebo; 2:1), double-blind study at Atopic Dermatitis Research Network centers. Bioassays were performed at multiple time points: S aureus and virulence factor quantification, 16s ribosomal RNA microbiome, serum biomarkers, skin transcriptomic analyses, and peripheral blood T-cell phenotyping. At baseline, 100% of participants were S aureus colonized on the skin surface. Dupilumab treatment resulted in significant reductions in S aureus after only 3 days (compared to placebo), which was 11 days before clinical improvement. Participants with the greatest S aureus reductions had the best clinical outcomes, and these reductions correlated with reductions in serum CCL17 and disease severity. Reductions (10-fold) in S aureus cytotoxins (day 7), perturbations in TH17-cell subsets (day 14), and increased expression of genes relevant for IL-17, neutrophil, and complement pathways (day 7) were also observed. Blockade of IL-4 and IL-13 signaling, very rapidly (day 3) reduces S aureus abundance in subjects with AD, and this reduction correlates with reductions in the type 2 biomarker, CCL17, and measures of AD severity (excluding itch). Immunoprofiling and/or transcriptomics suggest a role for TH17 cells, neutrophils, and complement activation as potential mechanisms to explain these findings.

Influence of face masks on the subjective impairment at different physical workloads

To quantify the subjective and cognitive impairment caused by wearing face masks at work, 20 men and 20 women (median age 47 years, range 19–65) were tested under different ergometer workloads while wearing surgical mask, community mask, FFP2 respirator or no mask in a randomized and partially double-blinded design. Masks were worn also at the workplace for four hours. Subjective impairment was recorded by questionnaires. Cognitive performance was tested before and after the workplace examination. Subjective feeling of heat, humidity, and difficult breathing increased with rising physical exertion and wearing time for all three mask types, most notably for FFP2. Even when blinded, participants with FFP2 reported difficult breathing already at rest. During physical exertion, individuals with low tolerance to discomfort reported significantly stronger impairment (OR 1.14, 95% CI 1.02–1.27). Regarding light work, older subjects (OR 0.95, 95% CI 0.92–0.98) and women (OR 0.84, 95% CI 0.72–0.99) showed significantly lower and atopic subjects stronger impairment (OR 1.16, 95% CI 1.06–1.27). No significant influence of mask wearing was detected on cognitive performance. Wearing a mask had no effect on cognitive performance, but led to discomfort which increased with physical exertion and wearing time. Individuals who tolerate discomfort poorly felt more impaired by wearing a mask during physical exertion.

1599 Rapid reduction in S. aureus in atopic dermatitis subjects following dupilumab treatment

1599 Rapid reduction in S. aureus in atopic dermatitis subjects following dupilumab treatment

Association between Sex-Related ALOX5 Gene Polymorphisms and Lung Atopy Risk.

Atopy is an exaggerated IgE-mediated immune response to foreign antigens in which metabolic abnormalities of the leukotrienes (LTs) pathway play a crucial role. Recent studies have described sex as a key variable in LT biosynthesis, partly explaining why treatment with anti-LT drugs in atopic subjects leads to better control of symptoms in women. In addition, variability in LT production is often associated with single nucleotide polymorphisms (SNPs) in the arachidonate 5-lipoxygenase (ALOX5) gene, which encodes the leukotriene-synthesizing enzyme machinery, 5-lipoxygenase (5-LO). This study aimed to investigate whether two SNPs of ALOX5 are implicated in sex differences in allergic diseases in a prospective cohort of 150 age- and sex-matched atopic and healthy subjects. Rs2029253 and rs2115819 were genotyped using allele-specific RT-PCR, and serum levels of 5-LO and LTB4 were measured by ELISA. Both polymorphisms are significantly more common in women than in men, and their influences on LT production vary as a function of sex, leading to a decrease in men's and an increase in women's serum levels of 5-LO and LTB4. These data represent a new resource for understanding sex-related differences in lung inflammatory diseases, partly explaining why women are more likely to develop allergic disorders than men.

Patients with a history of atopy have fewer cutaneous melanomas than those without atopy: a cross-sectional study in 496 patients at risk of skin cancers.

The connection between atopy and skin cancers may be related to the stimulation of protective immune response, for example, through autoreactive immunoglobulin-E (IgE), or to the predisposition to carcinogenesis through chronic inflammation. The aim of this study was to investigate whether a past or present atopic disorder is associated with cutaneous photodamage, pigment cell nevi and skin cancers. For this, adult subjects at risk of any type of skin cancer (aged 21-79 years, 250 males, 246 females, 94 with immunosuppression) were examined for past or present malignancies in skin and extracutaneous site (ECS), photodamage, nevi, past or present atopic disorder in skin or mucus membranes, and possible other cancer-related factors. No association between atopy and photodamage, keratinocyte carcinomas or nevus count was found. Instead, there were fewer subjects with melanoma in 171 atopic (14.6%) than in 325 nonatopic subjects (22.2%) ( P = 0.044), and the investigator-estimated risk class of skin cancers was lower in atopic than nonatopic subjects. In all subjects, the multivariate odds ratio (OR) for melanoma was 0.583 ( P = 0.046; 95% confidence interval, 0.343-0.990) in atopic subjects, but in immunocompetent subjects, the reduced risk was confined to mucus membrane atopy (OR, 0.417; P = 0.020). Also, there were fewer subjects with malignancy in ECS in atopic (8.8%) than nonatopic subjects (15.7%) ( P = 0.031). No association between serum total IgE and skin cancers, photodamage, nevi or malignancies in ECS was found. In conclusion, the atopy, especially mucus membrane atopy, is associated with lower percentages of subjects with a history of melanoma.

A Single-Period, Single-Dose Study of the Pharmacokinetics of Epinephrine After Administration of Intranasal ARS-1 to Pediatric Subjects with a History of Systemic Allergic Reaction

An epinephrine nasal spray (ARS-1) is being developed as a needle-free alternative to autoinjectors for the emergency treatment of systemic allergic reactions including anaphylaxis in children and adults. This study aims to assess the pharmacokinetics of epinephrine after intranasal (IN) administration of ARS-1 in pediatric atopic allergy subjects.

Covid-19 Histamine theory: Why antihistamines should be incorporated as the basic component in Covid-19 management?

Covid-19 Histamine theory: Why antihistamines should be incorporated as the basic component in Covid-19 management?

Identification of carboxymethyl (CM)-binding proteins derived from Lolium multiflorum pollen extract and antibody reactivity in Brazilian allergic patients.

Lolium multiflorum grass is the major pollen allergen source in the southern region of Brazil, but most of its allergens remain poorly characterized. The aim of this study was to investigate antibody reactivity to L. multiflorum crude and carboxymethyl-ligand extracts in allergic patients and healthy individuals. Ion exchange carboxymethyl (CM) chromatography (CM-Sepharose) was used to isolate proteins (S2) from L. multiflorum crude extract (S1), which were assessed by SDS-PAGE. S1- and S2-specific IgE and IgG4 levels were measured by ELISA using sera from 55 atopic and 16 non-atopic subjects. Reactive polypeptide bands in S1 and S2 were detected by immunoblotting, and the most prominent bands in S2 were analyzed by mass spectrometry (MS-MS). Similar IgE and IgG4 levels were observed to both S1 (IgE median absorbance: 1.22; IgG4 median absorbance: 0.68) and S2 (IgE median absorbance: 1.26; IgG4 median absorbance: 0.85) in atopic subjects. S1 and S2 had positive correlations for IgE and IgG4 (IgE: r=0.9567; IgG4: r=0.9229; P<0.0001) levels. Homology between S1 and S2 was confirmed by IgE (84%) and IgG4 (83%) inhibition. Immunoblotting revealed that the 29-32 kDa band was recognized by 100% of atopic subjects in both S1 and S2. MS-MS analysis identified similarity profile to groups 1 and 5 grass allergens. This study revealed that carboxymethyl-ligand fraction played an important role for pollen allergy diagnosis by containing clinically relevant allergens and constituted a promising candidate for allergen-specific immunotherapy.

Timing of Blood Sample Processing Affects the Transcriptomic and Epigenomic Profiles in CD4+ T-cells of Atopic Subjects.

Optimal pre-analytical conditions for blood sample processing and isolation of selected cell populations for subsequent transcriptomic and epigenomic studies are required to obtain robust and reproducible results. This pilot study was conducted to investigate the potential effects of timing of CD4+ T-cell processing from peripheral blood of atopic and non-atopic adults on their transcriptomic and epigenetic profiles. Two heparinized blood samples were drawn from each of three atopic and three healthy individuals. For each individual, CD4+ T-cells were isolated from the first blood sample within 2 h (immediate) or from the second blood sample after 24 h storage (delayed). RNA sequencing (RNA-Seq) and histone H3K27 acetylation chromatin immunoprecipitation sequencing (ChIP-Seq) analyses were performed. A multiplicity of genes was shown to be differentially expressed in immediately processed CD4+ T-cells from atopic versus healthy subjects. These differences disappeared when comparing delayed processed cells due to a drastic change in expression levels of atopy-related genes in delayed processed CD4+ T-cells from atopic donors. This finding was further validated on the epigenomic level by examining H3K27 acetylation profiles. In contrast, transcriptomic and epigenomic profiles of blood CD4+ T-cells of healthy donors remained rather unaffected. Taken together, for successful transcriptomics and epigenomics studies, detailed standard operation procedures developed on the basis of samples from both healthy and disease conditions are implicitly recommended.

Tonsillar transcriptional profiles in atopic and non-atopic subjects.

Emerging research suggests that local lymphatic tissue such as tonsils have important role in regulating the immune responses. However, allergen sensitization-induced alterations in transcriptome of tonsils are not known. To examine the key differences in tonsillar gene expression between atopic and non-atopic subjects and further by type of sensitization. RNA-sequencing was performed on 52 tonsillar samples from atopic and non-atopic tonsillectomy patients. Sensitization to common food- and aero-allergen was defined by allergen specific IgE. Following groups were studied: (1) aero- and food-allergen sensitized (AS+FS) versus non-sensitized (NS), (2) aeroallergen-sensitized (AS) versus food-allergen sensitized (FS), (3) AS versus NS, (4) FS versus NS. Bioinformatics analysis was done using DESeq2(v3.10.2), WGCNA and GATK pipeline in R software (v3.3.1). Protein-protein interaction network was made from String database. We studied 13 aeroallergen-sensitized, 6 food-allergen sensitized, 4 both food-and aero-allergen-sensitized and 29 non-sensitized tonsillectomy patients. Overall, 697 unique differentially expressed genes (DEGs) were detected in all sensitized subgroups including chemokines (CXCL2, CXCL8, CXCL10, CXCL11), IL-20RA, MUC1 and MUC20. When comparing different groups, the gene expression profiles overlapped except the AS versus FS group comparison, suggesting significantly different gene expression between the two sensitization subgroups. Furthermore, aeroallergen-sensitized subjects had more prominent immune responses compared with non-sensitized and food-allergen sensitized subjects including gene expression for IL-17 pathway and Toll-like receptor signalling pathway. Allergic sensitization is associated with extensive tonsillar transcriptomic alterations and changes in immune related genes and pathways. Distinct differences were found between aero-allergen and food-allergen sensitization.

519 Rapid reduction in S. aureus & cytotoxins in dupilumab treated atopic dermatitis subjects

Atopic dermatitis (AD) severity correlates with S. aureus (SA) colonization and barrier dysfunction. To address the importance of IL-4&-13 on these parameters, the Atopic Dermatitis Research Network designed a 6wk, RDBPC trial (Dupilumab[DPL]:placebo/2:1) with sampling (at 0, 3, 7, 14, 21, 28 & 42 days [d]) to quantify SA, barrier and severity (EASI, NRS, IGA & SCORAD). Seventy-two moderate-severe adult AD subjects were randomized. There was a >7-fold reduction in SA (qPCR) on lesional (L) skin in DPL vs placebo group (1o endpoint [28d];P<0.001).

299 Oral difelikefalin improves itch and inflammatory biomarkers in atopic dermatitis subjects with moderate-to-severe pruritus

Pruritus is the most frequent and burdensome atopic dermatitis (AD) symptom and can exacerbate disease via the itch-scratch cycle. Difelikefalin (DFK), a kappa-opioid receptor (KOR) agonist is approved for moderate-to-severe pruritus in adults with CKD undergoing hemodialysis. DFK blocks pruritic signaling through peripheral sensory neurons and may have anti-inflammatory activity. We tested the impact of DFK on pruritus-related and inflammatory transcriptomes of AD patients. In a phase 2 clinical study, subjects with AD and moderate-to-severe pruritus were randomized (1:1:1:1) to receive oral twice-daily DFK (3 doses) or placebo for 12 wk. A substudy (n=40) characterized effects of DFK on pruritus- and AD-related gene expression using baseline and wk 12 skin biopsies. Gene expression was measured using RNA-sequencing and TaqMan Low-Density Array qualitative polymerase chain reaction. Data from DFK groups were pooled. DFK altered expression of multiple individual pruritus- and AD-related genes. Gene set variation analysis confirmed downregulation of pruritus-related genes (eg, IL-31, TRPV2) and the Th2 pathway following 12 wk treatment with DFK, but not placebo. Changes in gene expression of pruritus- and immune-related genes significantly correlated with skin improvement for DFK-treated subjects. DFK downregulated expression of key genes implicated in pruritus and AD inflammation. Reports demonstrate an anti-pruritic effect of DFK in AD and other chronic itch conditions. DFK is a promising therapy for AD-related pruritus and may provide anti-inflammatory benefit by impacting the itch-scratch cycle.