Clinical Reviews in Allergy & Immunology最新文献

Airway remodeling, a hallmark of asthma, involves structural and functional changes in the airways including extracellular matrix (ECM) deposition, airway smooth muscle (ASM) cell hypertrophy and hyperplasia, epithelial and fibroblasts remodeling, and mitochondrial dysfunction driven by chronic inflammation. The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor commonly known for mediating xenobiotic responses, has recently emerged as a key regulator of cellular processes implicated in airway remodeling. This review explores the multifaceted role of AhR in modulating proliferation, migration, ECM remodeling, contraction, and mitochondrial homeostasis across various airway structural cell types. Based on recent studies, we highlight how AhR exerts anti-proliferative effects in ASM, epithelial, and fibroblasts, modulates calcium signaling to influence contraction, and regulates ECM turnover via transforming growth factor-β and matrix metallopeptidase pathways. Additionally, the dual, ligand- and context-dependent nature of AhR activation is emphasized, with both protective and detrimental outcomes observed depending on the specific agonist and disease conditions. Collectively, this review underscores the therapeutic potential of targeting AhR in airway remodeling.

Advances in the understanding of atopic dermatitis (AD) pathogenesis have driven the development of innovative systemic therapies targeting key immunologic pathways. This systematic review summarizes current evidence on the impact of biologic agents, Janus kinase (JAK) inhibitors, and other emerging treatments on AD-related biomarkers and their correlation with clinical outcomes. A comprehensive literature search was conducted across PubMed, Embase, Scopus, and Web of Science for studies published between 2014 and 2024. Eighty studies met the inclusion criteria. Dupilumab was the most extensively investigated therapy, followed by tralokinumab, JAK inhibitors, and novel agents such as amlitelimab, stapokibart, and tezepelumab. Across drug classes, consistent reductions in CCL17/TARC, LDH, and total IgE levels were observed, generally paralleling clinical improvement in EASI and SCORAD scores. Transcriptomic and proteomic analyses revealed normalization of Th2/Th22 inflammatory signatures and restoration of barrier-related gene expression, while microbiome studies showed a reduction in Staphylococcus aureus colonization. Despite these advances, the heterogeneity of study designs and analytical techniques limits the comparability of results. CCL17 and LDH currently represent the most reliable biomarkers associated with disease severity and treatment response, although their limited specificity restricts clinical applicability. Future research should aim to validate integrated biomarker panels combining immunologic, transcriptomic, and microbiomic data to enable precision medicine approaches in atopic dermatitis management.

This study aimed to establish an exposure-response model for IL-17 A inhibitors to predict the clinical efficacy of novel agents based on in vitro potency and pharmacokinetic parameters, guiding the development of new IL-17 A-targeting therapies. A systematic literature search was conducted in PubMed, Cochrane Library, and Embase to identify randomized controlled trials of three FDA-approved IL-17 A inhibitors: secukinumab, ixekizumab, and bimekizumab. Primary endpoints included PASI 75 and PASI 90. Pharmacokinetic parameters were extracted from FDA and EMA review documents, while the half-maximal inhibitory concentration (IC₅₀) values came from published studies. An exposure-response model was developed to characterize treatment effects in moderate-to-severe plaque psoriasis and externally validated using clinical data of xeligekimab. A total of 30 clinical trials involving 12,491 subjects were included. The model accurately described the time-effect characteristics of the PASI 75/90 response rates of the three IL-17 A inhibitors. Average drug concentration (C_av) was the most relevant exposure metric. The IC₅₀ value significantly influenced exposure-response outcomes, and lower IC₅₀ values required lower C_av for comparable efficacy. External validation showed high predictive accuracy for xeligekimab. A reference table was also constructed to estimate required doses based on IC₅₀ and desired therapeutic targets, facilitating rational dose selection. Based on existing pharmacokinetic and clinical efficacy data of IL-17 A inhibitors, this study successfully developed a streamlined and accurate exposure-response model, offers a practical tool for efficacy prediction and dose optimization in the development of novel agents targeting IL-17 A.

Background: Peanut allergy is a chronic IgE-mediated disease with potentially life-threatening consequences. While several immunotherapeutic strategies have emerged, including oral immunotherapy (OIT), omalizumab (OMA)-based therapies, and probiotic and peanut oral immunotherapy (PPOIT), the comparative effectiveness of these interventions remains unclear. This study aimed to evaluate the relative efficacy and safety of combined and standalone oral immunotherapies for peanut allergy using a Bayesian network meta-analysis (NMA).

Methods: A systematic literature search was conducted in PubMed, EMBASE, and Web of Science up to March 2025. We included randomized controlled trials (RCTs) involving patients with IgE-mediated peanut allergy who received OIT + OMA, OMA monotherapy, OIT alone, or PPOIT. Outcomes included low-dose and high-dose desensitization, sustained unresponsiveness (SU), and safety outcomes (adverse events, AEs). The risk of bias was assessed using RoB 2. Analyses were performed using R software (version 4.4.3) with Bayesian NMA methods.

Results: Nineteen RCTs involving 2040 participants were included. Based on Probability Scores (P-scores), OIT + OMA demonstrated the highest efficacy for both low- (P-score: 97.20%) and high-dose desensitization (96.69%), followed by PPOIT (70.15% and 51.16%), OIT third (64.40% and 52.72%), and OMA fourth (75.29% and 71.21%). PPOIT and OIT showed moderate efficacy for SU. OIT was associated with a higher frequency of AEs compared with placebo.

Conclusions: Combination and modified immunotherapies may offer improved efficacy and safety profiles, though results should be interpreted in the context of limited data and study heterogeneity.

Systemic lupus erythematosus (SLE) is a chronic, heterogeneous autoimmune disease with a strong female predisposition, characterized by multi-organ inflammation and damage. Its pathogenesis arises from a complex interplay of genetic susceptibility, epigenetic alterations, hormonal influences, and environmental triggers. This confluence drives a sustained loss of self-tolerance and profound immune dysregulation. Innate immune dysfunction, featuring unchecked type I interferon (IFN) production and defective clearance of cellular debris, exposes autoantigens. Concurrent adaptive immune defects include a breakdown of B and T cell tolerance, leading to pathogenic autoantibody production, dysregulated cytokine networks, and aberrant lymphocyte interactions. These processes culminate in tissue injury via immune complex deposition and direct cellular effects. This review synthesizes current understanding of these multifaceted immunological mechanisms in SLE, underscoring how their delineation has informed the development of targeted biologic therapies and highlighting the ongoing need for translational research to improve patient outcomes. Furthermore, emerging insights into the heterogeneity of immune pathways among patients emphasize the potential for personalized treatment approaches tailored to specific molecular profiles.

SARS-CoV-2 infection may induce long-term immune dysregulation; however, its contribution to the development of autoimmune disease remains disputed. We aim to quantify the relative risk of new-onset autoimmune diseases following COVID-19 and its modifiers through a systematic review and meta-analysis of population-based cohort studies. MEDLINE, Embase, Cochrane Library, and Web of Science were searched to March 31, 2025, for cohort studies comparing individuals with and without confirmed COVID-19. Random-effects meta-analysis estimated pooled hazard ratios (HRs) with 95% CIs. Subgroup analyses examined the severity of acute COVID-19, vaccination status, and demographics. Risk of bias was evaluated with the Newcastle-Ottawa Scale, certainty of evidence with GRADE, and publication bias with funnel plots and Egger's test. The review protocol was prospectively registered in PROSPERO (CRD42025646186). Seventeen cohort studies, including over 250 million person-years, were included. COVID-19 was associated with a 49% increased risk of new-onset autoimmune-related diseases (AIRD; HR = 1.49, 95% CI: 1.21-1.83; p = 0.0002). Significant associations (p < 0·05) were observed for 17 of 23 outcomes, with the strongest risks in antiphospholipid syndrome (HR = 2·16), ANCA-associated vasculitis (HR = 2·15), mixed connective tissue disease (HR = 2·12), and immune thrombocytopenic purpura (HR = 1·87). Risk was higher after severe infection (HR = 1.70), but was reduced in vaccinated individuals (HR = 0.56, compared to 1.42 in unvaccinated individuals). The certainty of evidence was moderate for conditions with large effect sizes, but low overall, reflecting heterogeneity across studies and the non-randomized design of the included studies. SARS-CoV-2 infection increases the risk of autoimmune diseases, particularly those affecting vascular and connective tissue. Risk is amplified by severe infection and attenuated by vaccination. These findings highlight the necessity of vaccination and targeted follow-up in severe COVID survivors.

Food allergy is an increasing public health concern characterized by inappropriate Th2-driven immune responses to otherwise harmless food antigens, leading to IgE-mediated hypersensitivity. Current management strategies rely on allergen avoidance and emergency interventions, which fail to address the root cause of immune dysregulation. Given the central role of helper T cells, particularly Th2 and regulatory T cells (Tregs), this systematic review evaluates the efficacy, safety, and immunological effects of three T cell-targeted allergen-specific immunotherapies: oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT). Thirteen studies, comprising 14 study arms, from four databases were included following PRISMA 2020 guidelines and PICOS-based selection. Based on the study design, RoB 2 and ROBINS-I tools were used to evaluate risk of bias. OIT demonstrated strong clinical and immunological outcomes, with high desensitization and sustained unresponsiveness (SU) rates, increased FOXP3⁺ Tregs, and suppression of Th2 cytokines (IL-4, IL-5, IL-13). SLIT showed moderate immunomodulatory effects with better tolerability, while EPIT provided the safest profile but limited T cell reprogramming. Overall, this review highlights the therapeutic potential of targeting T cells in food allergies and supports the use of OIT as the most effective current strategy, despite a higher risk of adverse events. While SLIT and EPIT remain promising, particularly in pediatric populations, further research is needed to enhance durability, personalize treatments, and combine immunotherapies with adjuncts such as biologics or Treg-promoting agents to achieve lasting immune tolerance. PROSPERO registration ID: CRD420251012358.