Interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP) released in the airways are believed to be associated with a greater risk of childhood-onset asthma. The aim of this study was to measure the release of IL-33 and TSLP into the airways of children and young people (CYP) during asthma attacks and compare these alarmin-cytokine levels with stable disease patients and non-asthmatic controls. We conducted a prospective observational case-control feasibility study, where we measured the levels of IL-33 and TSLP using high sensitivity immunoassays in the airways of children and young people (CYP) during asthma attacks, stable disease patients and non-asthmatic control individuals. Median concentrations of sputum IL-33 and TSLP from acute asthmatics were 3.4 and 17.7 times higher, respectively, in acute asthmatics compared to stable asthmatic children. Sputum IL-33 and TSLP were not different in the stable asthma group compared to non-asthmatic controls. IL-33 and TSLP were significantly elevated during acute severe asthma attacks and could potentially drive further airway inflammation and remodelling during asthma attacks in children. Results support further clinical evaluation of anti-TSLP and anti-IL-33 biologic therapeutics for preventing or reducing the frequency of asthma attacks in children.

Periodontal disease results from dysbiotic oral biofilms and the host's inflammatory response. Given the limitations of conventional therapies, this study aimed to evaluate the efficacy and safety of Weissella cibaria CMU (OraCMU) in improving gingival inflammation in individuals with gingivitis and incipient periodontitis. In this randomized, double-blind, placebo-controlled trial, 80 participants received either OraCMU tablets (2.0 × 108 CFU/g; n = 40) or placebo (n = 40) twice daily for 8 weeks. The primary outcome was the gingival index (GI), and secondary outcomes included bleeding on probing (BOP), probing depth, clinical attachment level, gingival recession, plaque index, inflammation-related proteins, and oral microbiota. Clinical parameters were assessed at six preselected index teeth (#16, 12, 24, 32, 36, and 44). At week 8, the probiotic group showed significantly greater reductions in GI (-0.19 ± 0.03 vs. -0.08 ± 0.04; P = .035) and BOP (-7.74 ± 1.54 vs. -2.82 ± 1.60; P = .030) compared with the placebo group. Inflammatory markers, including fibroblast growth factor-5 (P = .003), thymic stromal lymphopoietin (P = .017), and the receptor activator of nuclear factor κB ligand/osteoprotegerin ratio (P = .021), were significantly decreased. The levels of Porphyromonas gingivalis (P = .001), Treponema denticola (P = .005), and Prevotella intermedia (P = .046) were also significantly reduced, while Weissella increased (P < .001) in the probiotic group. Eight-week supplementation with OraCMU improved gingival health and modulated the oral microbiota and inflammatory response. No serious adverse events were reported during the study period. These findings support the potential clinical utility of OraCMU as a probiotic adjunct for managing gingivitis.

Thymic stromal lymphopoietin (TSLP) - pro-inflammatory cytokine and antimicrobial peptide.

GR2002 is a novel bispecific antibody targeting dual epitopes on thymic stromal lymphopoietin (TSLP). We aimed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of GR2002 in healthy Chinese adults. In this randomized, double-blind, placebo-controlled, dose-escalation, phase 1 trial of GR2002, healthy adults were enrolled and assigned to one of five dose cohorts. Within each cohort, participants were randomized (4:1) to receive a single subcutaneous dose of GR2002 (35, 70, 140, 280, or 420 mg) or placebo and were followed for 85 days. The primary endpoints included safety and tolerability. Secondary endpoints comprised PK, PD, and immunogenicity. Fifty eligible subjects were enrolled and randomized to receive either GR2002 (n = 40) or placebo (n = 10). A total of 92 treatment-emergent adverse events (TEAEs) were reported, with comparable incidence between the GR2002 and placebo groups. TEAEs were generally mild to moderate in severity and did not exhibit dose dependency. The most common treatment-related adverse event was upper respiratory tract infection, occurring in 7/40 (17.5%) participants in the GR2002 group and 2/10 (20%) in the placebo group. GR2002 displayed linear PK across the dose range tested, with a mean half-life ranging from 26.0 to 58.9 days. Dose-dependent reductions in serum TSLP levels from baseline were observed in the 140-420 mg dose groups. Anti-drug antibodies were detected in six subjects (15%) following GR2002 administration. Single-dose subcutaneous administration of GR2002 demonstrated favorable safety and tolerability, linear PK, and low immunogenicity. These findings warrant the subsequent clinical development of GR2002.

QX008N, an Anti-TSLP Monoclonal Antibody: Pharmacokinetics, Tolerability, and Immunogenicity in Healthy Chinese Subjects.

IL-1 family members as regulators of lymphoid type-2 immunity in cancer.

This systematic review aims to evaluate the effectiveness of Tezepelumab, a monoclonal antibody targeting the thymic stromal lymphopoietin, in patients affected by chronic rhinosinusitis with nasal polyposis, both with and without comorbid asthma. A systematic search of the literature was conducted across PubMed, SCOPUS, and Google Scholar databases until April 2025. Studies were selected based on predefined inclusion criteria, focusing on adult patients with clinically diagnosed chronic rhinosinusitis with nasal polyps who received Tezepelumab treatment for at least four weeks and reported validated clinical outcomes. Studies involving patients receiving prior standard treatment and comorbid asthma were included. Outcome measures included sinonasal symptom scores, imaging scores, pulmonary function tests, quality of life assessments, systemic corticosteroid use, and the need for surgical intervention. Study selection, data extraction, and quality assessment were conducted independently by two reviewers. Out of 221 screened records, three randomized controlled trials involving a total of 691 patients met the eligibility criteria. Tezepelumab treatment resulted in significant improvements in nasal symptom scores, including reductions in nasal congestion and loss of smell, as well as improved quality of life and sleep-related symptoms. Objective assessments showed a reduction in polyp size and radiological scores, with fewer patients requiring systemic corticosteroids or surgical intervention compared to placebo. Improvements were also observed in lung function and disease control among patients with comorbid asthma. The effect size exceeded minimal clinically important difference thresholds across key outcome measures. Tezepelumab demonstrated consistent and clinically meaningful benefits in the treatment of chronic rhinosinusitis with nasal polyps, including symptom relief, reduced polyp burden, and decreased need for corticosteroids or surgery. Its upstream mechanism offers potential advantages over existing biologic therapies. Further long-term and real-world studies are needed to confirm its role in clinical practice and define ideal patient selection strategies.

BackgroundInterleukin -17 (IL-17), particularly IL-17A, thymic stromal lymphopoietin (TSLP), interferon gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), IL-2, IL-6, IL-23, and IL-31 play a significant role in the pathogenesis of various chronic inflammatory and autoimmune skin diseases.MethodWe conducted an assessment of plasma levels of interleukins IL-17A, TSLP, IFN-γ TNF-α, IL-2, IL-6, IL-23, and IL-31 in 89 atopic dermatitis (AD) patients and in 34 healthy individuals as a control group. The group of AD patients consisted of 27 patients treated with dupilumab for moderate and severe form (15 men, 12 women, mean age of 44.8 years) and 62 AD patients suffering from moderate and severe form without any systemic treatment (35 women,27 men, mean age of 46.3 years). The control group consisted of 34 healthy subjects (22 men, 12 women, mean age of 43.3 years). For screening analysis of plasma levels of cytokines the performance assay Human cytokine Luminex was used. Blood samples were unstimulated and stimulated with phorbol myristate acetate and ionomycin. The levels of IL-17A, TSLP, IFN-γ, TNF-α, IL-2, IL-6, IL-23, and IL-31 were compared in AD patients with the results in control group. Nonparametric Kruskal-Wallis analysis of variance with post-hoc Dunn’s test with Bonferroni modification of significance level was used for statistical analysis.ResultsUnder unstimulated conditions we found these significant differences:1) Higher IL-17A and TNF-α in dupilumab-treated AD patients vs. healthy controls, suggesting residual Th17 and pro-inflammatory activity despite Th2 blockade. 2) TSLP elevated in both groups of AD patients indicating persistent epithelial barrier stress. 3) Low IFN-γ in both groups of AD patients is consistent with Th2 dominance. Under stimulated conditions we found these significant differences: 1) Lower IL-23 in both groups of AD patients vs. healthy controls suggesting possible impaired Th17 axis activation. 2) Lower IL-2 in patients without systemic treatment vs. healthy controls indicating reduced T-cell activation capacity without biologic therapy. 3) Higher IL-6 in both groups of AD patients vs. healthy controls reflecting ongoing innate/inflammatory activation under both conditions.ConclusionDupilumab effectively suppresses Th2 signaling but does not fully normalize immune balance; residual Th17 and innate activity persists. Elevated TSLP and IL-6 suggest that epithelial stress and innate immune activation remain key drivers. Reduced IL-23 and IL-2 under stimulation indicate altered adaptive immune responsiveness in AD patients.

Objective Tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), is effective in treating severe asthma. However, the factors predicting the therapeutic efficacy of tezepelumab remain unclear. This study examined the background and serum cytokine levels of patients with severe asthma who were treated with tezepelumab to identify the factors that predict therapeutic efficacy. Methods Eighteen patients with severe asthma who received tezepelumab were enrolled in this small cohort. Blood tests, pulmonary function tests, and questionnaires were administered at baseline and after 1, 2, 4, 6, and 12 months of treatment. Responders, i.e. participants with a Global Evaluation of Treatment Effectiveness score of “good” or “excellent” 4 months after treatment initiation, were included in the analysis. Results There were twelve responders and six non-responders. Responders were older than non-responders, and treatment was significantly more effective in patients with type 2 asthma than in those with non-type 2 asthma. At baseline, responders had significantly lower levels of PDGF-BB and ST2/IL-33R than non-responders (PDGF-BB: responders, 7802.4 ± 1658.8 pg/mL, non-responders, 9530.0 ± 1498.5 pg/mL, p = 0.048; ST2/IL-33R: responders, 13732.8 ± 4472.3 pg/mL, non-responders, 22168.5 ± 5699.3 pg/mL, p = 0.003). Conclusions Tezepelumab was more effective in older patients with type 2 asthma than in those with non-type 2 asthma. Furthermore, baseline serum ST2/IL-33R levels, a potential target for new asthma treatments, may be useful in predicting the efficacy of tezepelumab. However, larger studies are needed to validate our findings.

Homeostatic maturation programs drive human cDC2s into a tolerogenic state.

BACKGROUND: This study aims to address this knowledge gap through comprehensive assessment of clinical and functional changes in asthma patients using various nicotine consumption methods. AIM: To evaluate the impact of different types of smoking devices (conventional cigarettes, ENDS, HTPs) on asthma course and control, lung function, quality of life, and inflammatory profile in patients aged 18–45 years. METHODS: An open observational study was conducted at Moscow City Clinical Hospital No. 24. Inclusion criteria: age 18–45 years, asthma diagnosis duration ≥12 months. Exclusion criteria: acute respiratory viral infection, pregnancy, chronic obstructive pulmonary disease, other lung diseases. Primary endpoints: asthma control (ACT questionnaire), quality of life (AQLQ questionnaire), forced expiratory volume in 1 second (FEV₁), inflammatory biomarkers (blood eosinophils, eosinophil cationic protein (ECP), periostin, thymic stromal lymphopoietin (TSLP), interleukin-13 (IL-13)). Assessment methods included validated questionnaires, spirometry, fractional exhaled nitric oxide (FeNO) measurement, and laboratory blood analysis. RESULTS: The study included 153 patients (149 men, 4 women), mean age 22.14±3.09 years. Among them, 59 were non-smokers and 94 were smokers, with 56.4% of smokers being multi-users of various smoking devices. Smoking patients had worse asthma control by 2.7 points on the ACT scale (p0.001), FEV₁ lower by 4.5% (p0.05), and quality of life by AQLQ questionnaire lower by 0.83 points (p0.001) compared to non-smokers. A change in inflammatory phenotype was identified: ECP level was 18.3% lower (p0.05), blood eosinophils 10.3% lower, neutrophil level 14.3% higher (p0.01) in smokers. Elevated levels of periostin by 31.0% (p0.05) and TSLP by 73.5% (p0.05) were observed in smoking patients. Subgroup analysis by smoking device type (conventional cigarettes, ENDS, HTPs, their combinations) revealed no statistically significant differences (p0.05). CONCLUSION: All types of smoking devices have comparable negative effects on asthma control, lung function, and patients' quality of life, and lead to changes in inflammatory phenotype with reduced eosinophilic and enhanced neutrophilic components.

Microorganisms residing on the skin play a crucial role in maintaining both the integrity of the skin barrier and immune function. This study examined the effects of culture supernatants from canine-derived Bifidobacterium animalis subsp. lactis DS008 on canine keratinocytes in vitro. To induce cytokine production, canine progenitor epidermal keratinocytes (CPEK) were indirectly co-cultured with Malassezia pachydermatis using an insert well system to prevent direct cell-to-yeast contact, and CPEK were supplemented with 0.1%, 1%, and 10% of DS008 supernatants. mRNA expression levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-13, thymic stromal lymphopoietin (TSLP), IL-31, and keratin 10 were analyzed by real-time PCR. The protein concentrations of TSLP and IL-31 were measured by ELISA. Additionally, DS008 supernatants were applied to reconstructed canine epidermis (RCE) models exposed to lipopolysaccharide to evaluate changes in epidermal architecture. Treatment with DS008 supernatants showed significant reductions in mRNA expression of TNF-α, IL-13, TSLP, and IL-31, as well as decreased protein levels of TSLP and IL-31. Furthermore, keratin 10 mRNA expression was significantly increased, and RCE analysis demonstrated that DS008 supernatants ameliorated stratum corneum deformation. These findings suggest that postbiotics derived from canine-derived Bifidobacterium animalis subsp. lactis DS008 is a potential candidate with anti-inflammatory properties.

Nicotinamide adenine dinucleotide (NAD⁺) is essential for cellular metabolism, DNA repair, and stress responses. NAD+ is synthesized from nicotinamide, nicotinic acid (collectively termed niacin), and tryptophan. In humans, deficiencies in these nutrients result in pellagra, marked by dermatitis, diarrhea, and dementia. The dermatitis associated with pellagra typically manifests as photodermatosis in sun-exposed areas. This study examined the effects of NAD+ deficiency on skin homeostasis using epidermis-specific Nampt conditional knockout (cKO) mice. These mice displayed substantial NAD⁺ depletion, reduced poly(ADP-ribose) polymerase (PARP) activity, and increased DNA damage. Consequently, Nampt cKO mice developed spontaneous skin inflammation and epidermal hyperplasia. RNA sequencing and immunohistochemical analyses demonstrated increased interleukin-36 (IL-36) cytokine expression, suggesting that DNA repair-related genomic stress triggers keratinocyte-driven IL-36 production, which promotes inflammation. Furthermore, reduced collagen17A1 expression and elevated thymic stromal lymphopoietin (TSLP) levels were observed. NAD+ repletion by transdermal supplementation of nicotinamide mononucleotide (NMN) suppressed the rise of IL-36 levels and skin inflammation. These findings underscore the importance of Nampt-mediated NAD⁺ metabolism for epidermal stability and indicate that NAD⁺ depletion may contribute to IL-36-mediated skin inflammation, offering insights for therapeutic strategies in inflammatory skin disorders.

Aspirin-exacerbated respiratory disease (AERD) is characterized by chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs). Although high-dose aspirin therapy after desensitization (ATAD) and surgery are effective, adverse effects and high dropout rates limit its use. The emergence of biologics for asthma and/or CRSwNP entails rethinking the management of AERD. There is no consensus on choosing between ATAD and biologics. This systematic review evaluates current evidence on the role of biologics in the management of AERD, focusing on their potential to induce NSAID tolerance and proposing a management algorithm. A systematic literature search was conducted across PubMed, Embase, and Scopus up to March 2025. Studies were selected based on predefined criteria, excluding editorials, reviews, case reports, guidelines, and publications not in English. Data were extracted from clinical trials, real-world studies, and retrospective analyses. The various inflammatory pathways targeted by biologics included immunoglobulin E (omalizumab), subunit alpha of the interleukin 4 receptor (IL-4Ra) (dupilumab), IL-5/IL-5Ra (mepolizumab, benralizumab), and thymic stromal lymphopoietin (tezepelumab). These drugs have demonstrated efficacy in improving asthma and CRSwNP in AERD. The most consistent evidence seems to favor omalizumab and dupilumab for enhancing tolerance to NSAIDs. Although evidence remains inconclusive, the combination of ATAD and biologics may offer additive benefits in selected patients. Biologics represent a promising alternative in the management of AERD, particularly for patients with poor tolerance to aspirin. Further prospective, controlled studies are needed to define optimal treatment algorithms and identify biomarkers predictive of therapeutic response.

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and chronic airway inflammation, traditionally managed with inhaled bronchodilators and corticosteroids. However, a significant subset of patients exhibits suboptimal response to these inhaled therapies, and disease progression remains challenging to control effectively. Recent advances in understanding the inflammatory pathways underlying COPD have led to the development of biologic agents targeting critical cytokines and their receptors, including IL-4 receptor (IL-4R), IL-5, IL-5 receptor (IL-5R), IL-33, ST2, and thymic stromal lymphopoietin (TSLP). Emerging drugs such as JKN2401, TQC2731, and tezepelumab demonstrate promising therapeutic potential by modulating these specific inflammatory mediators. This review comprehensively summarizes the pathophysiological roles of these cytokines in COPD, the current progress in biologic drug development targeting these molecules, and the outcomes of recent clinical trials. By elucidating these novel therapeutic avenues, the article aims to provide a theoretical foundation and clinical guidance for precision medicine approaches in COPD management beyond conventional inhaled treatments.

Emerging evidence identifies platelets as active participants in inflammation beyond their traditional hemostatic function. Mast cells, tissue-resident granulocytes, are key players in innate immunity. Recent studies reveal dynamic bidirectional interaction between these two cell types. An IL33-driven feed-forward circuit has been described, in which mast cell-derived leukotriene C4 activates platelets through cysteinyl leukotriene receptor 2 (CysLT2R), whereas platelet-derived nucleotides subsequently enhance mast cell activation through P2Y1-dependent signaling. This reciprocal exchange redefines platelets and mast cells as cooperative amplifiers of type 2 inflammation rather than isolated effectors. The model challenges classical hierarchical views of immune signaling, proposing reciprocity where feedback strength, not stimulus persistence, determines inflammatory stability. Several mechanistic questions emerge, including the physiological magnitude of platelet-derived ATP/ADP flux in vivo, the spatial context of platelet-mast cell interactions within airway microenvironments, and whether other epithelial alarmins such as IL-25 and thymic stromal lymphopoietin (TSLP) engage similar pathways. Conceptually, this bilateral circuitry positions platelets as integral components of cytokine-driven networks that sustain allergic and asthmatic inflammation. Therapeutically, it suggests opportunities to target CysLT2R and P2Y1 signaling to locally dampen inflammatory amplification without impairing systemic hemostasis. In addition, platelets contribute to vascular leakage, shock, and tissue inflammation following cardiac surgery through perivascular mast cell activation mediated by platelet-activating factors. Moreover, mast cell and platelet-derived 5-hydroxyindoleacetic acid signal through the GPR35 receptor to promote eosinophil recruitment and fungal persistence during Cryptococcus neoformans infection. Collectively, these findings broaden our understanding of platelet function and underscore the importance of intercellular communication in maintaining or disrupting the balance between transient and chronic inflammation.

Environmental exposures are increasingly recognized as important drivers of ocular surface inflammation, yet their combined contribution to the onset, exacerbation, and clinical burden of allergic conjunctivitis (AC) has not been comprehensively synthesized. This systematic review evaluated the evidence linking air pollutants, aeroallergens, and indoor or occupational exposures with allergic conjunctivitis. The review was conducted according to PRISMA 2020 and AMSTAR-2 guidelines and registered in PROSPERO (CRD420251162399). PubMed, Web of Science, and Scopus were searched from inception to 18 September 2025. Two independent reviewers screened studies, extracted data, and assessed methodological quality using the MINORS tool. Owing to substantial heterogeneity, findings were synthesized narratively. Twenty-nine studies were included, encompassing more than three million outpatient visits. Consistent associations were observed between particulate matter, nitrogen oxides, sulfur dioxide, carbon monoxide, and ozone with increased AC incidence and symptom severity, with variations by age, sex, and season. Pollen and air pollutants frequently acted synergistically. Indoor exposures were associated with increased risk in children, while occupational settings demonstrated exposure-response relationships. Experimental studies identified mechanisms involving epithelial barrier disruption, NF-κB activation, and thymic stromal lymphopoietin signaling. Overall, environmental exposures substantially contribute to allergic conjunctivitis and may inform improved prevention and personalized clinical management.

Chronic rhinosinusitis (CRS) has aprevalence of up to 11% in Europe and the USA, making it one of the most common chronic diseases. Classification based on immunological endotypes is increasingly being integrated into the disease definition, particularly for chronic rhinosinusitis with nasal polyps (CRSwNP). Depending on the specific mechanisms underlying chronic tissue inflammation, different endotypes are characterized. Genetic and epigenetic changes in the mucosal immune system play asignificant role in this context. Identifying endotypes can help to better understand disease heterogeneity and develop personalized treatment approaches. In part1 of this publication, we discussed the immunological classifications of typeIV hypersensitivity reactions (T1-, T2-, and T3-endotypes), while part2 focused on typeV hypersensitivity reactions (epithelial barrier defects). The aim of part3 is to describe typeVI hypersensitivity immune reactions and highlight their implications for extended diagnostics and treatment. The European Academy of Allergy and Clinical Immunology (EAACI) recently published aposition paper presenting an updated nomenclature for immunological hypersensitivity reactions, now encompassing nine distinct immunological reaction types. The antibody-mediated reactions originally classified by Coombs and Gell as typesI, II, andIII have been expanded and described in greater detail. Direct cellular and inflammatory responses to chemical substances are defined as typeVI hypersensitivity reactions and are the focus of this third part of the publication series. In CRSwNP patients with typeVI hypersensitivity immune reactions, an imbalance between cyclooxygenase (COX) isoforms1 and2 can be observed. This imbalance is exacerbated by COX-1-inhibiting drugs, leading to reduced prostaglandin E2 (PGE2) synthesis and overproduction of leukotrieneC4 (LTC4) and PGD2. As aresult of the chronic mucosal inflammation, alarmins such as interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP) are released. These cytokines activate Th2 lymphocytes and type2 innate lymphoid cells (ILC2s), prompting the release of cytokines such as IL‑4, IL‑5, and IL-13. Expansion of the immunological classification to include typeVI hypersensitivity reactions represents an important step toward abetter understanding of the pathophysiology of CRSwNP. Identifying these specific reaction patterns-particularly those triggered by chemical substances-highlights the complexity of the underlying immune mechanisms and emphasizes the need for endotype-based diagnostics. Incorporating these insights into clinical practice allows for more targeted individualized therapies and marks another step toward personalized medicine in CRS.

Gut-lung axis: moxibustion's impact on short-chain fatty acids in various tissues of asthmatic rats.

Abstract Background Eosinophilic esophagitis (EoE) and celiac disease (CD) are autoimmune disorders involving the gastrointestinal tract with increasing prevalence. However, the association and prevalence of EoE in patients with CD remains unclear. Aims We aimed to conduct a systematic review and meta-analysis regarding the prevelence of EoE and CD given the recent publication of multiple new population and cohort based studies. Methods The MeSH terms “Eosinophilic Esophagitis” and “Celiac Disease” were used on PubMed to search for articles from database inception to May 2025. Two independent reviewers screened titles and abstracts, with a full-text review conducted for studies directly comparing EoE and CD. The primary outcome entailed the evaluation of an association between EoE and CD. Secondary outcomes included evaluation of shared pathophysiology and treatment of the conditions. A meta-analysis of the prevalence of EoE in patients with CD was performed using all applicable population-based studies with control group and single cohort studies. Statistical analysis was performed using Microsoft Excel Meta-Analysis workbook from the Erasmus Research Institute. Results In total, 136 articles were identified, and 39 studies underwent full-text review as these directly compared EoE and CD. 12 studies met the inclusion criteria for the meta-analysis: 5 comparative and 7 single-cohort studies. Across the five comparative studies, the pooled odds ratio for concurrent EoE and CD was 3.07 (95% CI 0.60–13.71; I2 = 98.9%), suggesting a trend toward increased risk, although with high heterogeneity. Among the seven single-cohort studies, the pooled prevalence of EoE among patients with CD was 3.8% (95% CI 1.4–7.3%; I2= 90.5%) under a random-effects model using the Freeman–Tukey double-arcsine transformation. This rate is much higher than the prevalence of EoE in the general population which is estimated at 0.1%. In terms of secondary outcomes: proposed pathophysiologic mechanisms linking EoE and CD include impaired gut membrane permeability and global regulatory T-cell dysfunction. Other inflammatory mediators such as IL-15 and thymic stromal lymphopoietin have been increasingly implicated in both conditions and may serve as potential therapeutic targets in the future. A retrospective study found no association between EoE and HLA-DQ2 and DQ8, alleles predisposing to CD, suggesting an unlikely genetic association between the two conditions. Currently, only a small subset of patients with EoE and CD achieve full clinical remission with gluten-free diets, while many report remission with an elemental diet. Conclusions This meta-analysis demonstrates an increased prevalence of EoE among patients with CD when compared to the general population. Proposed mechanisms linking the conditions may include epithelial barrier dysfunction and aberrant cytokine signaling. Funding Agencies NoneNil