Clinical Reviews in Allergy & Immunology最新文献

Asthma is a major chronic non-communicable respiratory disease, affecting over 300 million individuals globally, with an adult prevalence of 4.3%. Despite advances in individualized treatment, a subset of patients, particularly those with non-type 2 (non-T2) asthma, fails to achieve optimal disease control. Non-T2 asthma, characterized by steroid resistance and heterogeneous immune responses, remains a therapeutic challenge. Emerging evidence suggests that circadian rhythm disruption may modulate key pathological processes relevant to non-T2 asthma, including immune imbalance, epithelial barrier dysfunction, and impaired glucocorticoid sensitivity. This review investigates evidence of an association between circadian clock dysfunction and non-type 2 asthma pathogenesis, and proposes a hypothesis-driven framework to guide future studies. Chronotherapeutic strategies and clock-targeted interventions may offer promising avenues for future research and individualized treatment.

Objectives: This study aimed to use Bayesian network meta-analysis to compare the efficacy and safety of biologics for systemic lupus erythematosus (SLE). A comprehensive and systematic search of electronic databases (PubMed, Medline, Cochrane Library, EMBASE, Web of Science, CNKI, and WanFang Data) was conducted from 2014 to September 2024. Our study only included randomized controlled trials with full articles that enrolled adult SLE patients treated with biologics, in comparison with standard therapy. The primary efficacy endpoints were SLE Responder Index 4 (SRI4) and BICLA (BILAG-Based Composite Lupus Assessment). The safety endpoints were adverse events (AEs) and serious adverse events (SAEs). R 4.4.3 and RStudio were used to conduct the network meta-analysis. RevMan 5.4 was used to assess the included literature. 29 randomized controlled trials with a total of 13,712 patients met the inclusion criteria. The network meta-analysis indicated that compared with standard therapy, telitacicept (OR 5.2, 95% CI 1.4-20.0) demonstrated superior efficacy in achieving SRI4 response, deucravacitinib (OR 1.6, 95% CI 1.0-2.5), and anifrolumab (OR 1.6, 95% CI 1.3-2.0) all exhibited significant BICLA response in moderate-to-severe SLE patients. Regarding safety, it was observed that there were no significant statistical differences among the various treatment options. Cluster analysis revealed that deucravacitinib exhibited the best efficacy-safety profile. Deucravacitinib suggested a favorable profile between efficacy and safety. Telitacicept showed the most pronounced improvement in SRI-4 response, but was associated with higher rates of AEs and SAEs, whereas anifrolumab and deucravacitinib displayed advantages in reducing SAEs. For patients with elevated baseline IFN signatures, anti-type I interferon biologics such as anifrolumab and sifalimumab are recommended to maximize clinical benefits. The reliance on indirect comparisons necessitates cautious interpretation of these findings, so further research should prioritize direct head-to-head trials to validate the efficacy and safety profiles of these biologics.

Aquaporins (AQPs) are transmembrane proteins that facilitate the transport of water and small solutes across cell membranes. Their expression in organs such as the skin, lungs, gastrointestinal tract, and immune system has been implicated in the pathophysiology of various allergic diseases. Emerging evidence suggests that AQPs, particularly AQP1, AQP3, AQP4, AQP5, AQP7, and AQP9, are differentially regulated during allergic responses, contributing to symptoms such as mucosal hypersecretion, edema, and skin dryness. In atopic dermatitis, AQP3 overexpression correlates with increased transepidermal water loss, while in food allergy models, downregulation of AQP4 and AQP8 is associated with allergic diarrhea. In asthma, altered expression of AQP1, AQP3, and AQP5 has been linked to airway inflammation, eosinophil migration, and mucus production. The cAMP/CREB and NFκB signaling pathways have been identified as key regulators of AQP5 expression, providing potential therapeutic targets. Several experimental studies using herbal extracts have demonstrated anti-inflammatory effects mediated through upregulation of AQP1 and AQP5 and suppression of proinflammatory cytokines. A proposed integrative model suggests that AQPs participate in both the sensitization and effector phases of the allergic response, influencing antigen presentation, immune cell migration, and mediator release. Despite promising preclinical findings, human studies remain limited. Further clinical research is warranted to validate AQPs as biomarkers and therapeutic targets in allergic diseases, especially considering the increasing global prevalence of these conditions.

As a key epigenetic regulator, E3 ubiquitin-ligase ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) is essential for maintaining genomic stability. The aberrant activation of UHRF1 has been strongly implicated in cancer progression. Emerging evidence indicates that UHRF1 serves as a pivotal orchestrator of immune homeostasis. This review provides an overview of the impact of UHRF1 on both innate and adaptive immunity, highlighting its epigenetic and regulatory roles in the development and function of macrophages, T lymphocytes, and B lymphocytes. Crucially, the protective mechanisms of UHRF1 in autoimmune disorders while concurrently detailing its tumor-promoting functions are dissected. Finally, this review discusses the therapeutic challenges and future perspectives for targeting UHRF1 in autoimmune disorders and cancers.

With the acceleration of global urbanization, residential proximity to major roadways (RPMR) has been recognized as a significant threat to public health, while the association between road proximity and risks of allergic respiratory outcomes remains unclear. This study aims to evaluate the associations between RPMR and the risks of allergic respiratory outcomes. We conducted a systematic literature search for existing scientific literature from databases of PubMed, EMBASE, Web of Science, Cochrane, and Scopus. The study protocol was registered at PROSPERO (registration ID: CRD42024604182). Random effects models were applied to evaluate the associations between RPMR and the risks of allergic respiratory outcomes by calculating the pooled odds ratio (OR) and corresponding 95% confidence interval (CI). During the study periods, 55 eligible studies were included, comprising 373,320 participants. We found that a close RPMR (≤ 200 m) was associated with increased risks of asthma (OR = 1.23, 95% CI: 1.15, 1.31), wheezing (OR = 1.21, 95% CI: 1.12, 1.30), and rhinitis (OR = 1.22, 95% CI: 1.13, 1.32). In addition, we identified that the closer the RPMR, the higher the risks for allergic respiratory outcomes. The observed associations between RPMR and allergic respiratory outcomes were more pronounced among children and less urbanized areas than in adults and highly urbanized areas. Our study provides comprehensive evidence for the associations between RPMR and risks for allergic respiratory outcomes. The findings may contribute to the practical implications for urban planning and public health strategies to mitigate exposure to traffic-related pollution.

Inborn errors of immunity (IEIs) are traditionally viewed as monogenic disorders of the immune system, but mounting evidence indicates that they often have underappreciated impacts on the nervous system. We review the emerging intersection between IEIs and neurological diseases, spanning neurodevelopmental and neurodegenerative manifestations. We discuss how genetic overlaps between immunity and brain development-for example, defects in DNA repair, chromatin remodeling, or cytokine signaling-can lead to combined immunological and neurological phenotypes. Clinical data from patient cohorts highlight that a substantial subset of IEIs present with neurodevelopmental disorders (such as autism spectrum disorder, intellectual disability, or ADHD) and/or neurodegenerative diseases (such as progressive ataxia, motor regression, or cognitive decline). These comorbidities arise through diverse mechanisms, including direct roles of immune genes in neural development, the impact of chronic inflammation on the brain, and metabolic byproducts toxic to neural tissue. We illustrate these mechanisms with examples such as ataxia-telangiectasia (a DNA repair defect causing immunodeficiency and cerebellar degeneration) and DiGeorge syndrome (a developmental immunodeficiency often initially diagnosed as autism). The translational importance of these insights is profound-recognizing neurological involvement in IEIs can improve early diagnosis and multidisciplinary care, whereas a deeper understanding of immune-neural crosstalk opens avenues for novel therapies (such as targeted anti-inflammatory treatments or gene therapies that address both immune and neural dysfunction). By integrating immunology and neuroscience perspectives, this comprehensive review sheds light on the immune underpinnings of certain neurologic diseases and underscores the importance of collaborative management for patients at this complex interface.

Background: Inherited ARPC1B deficiency (ARPC1BD) is a rare autosomal recessive inborn error of immunity that manifests with allergic, infective, and autoimmune/inflammatory features. Only about three dozen patients with ARPC1BD have been reported in the literature thus far.

Methods: We describe 14 patients (ten families) with ARPC1BD from Nepal. Many of these patients have unique/rare clinical features that expand the phenotypic spectrum of ARPC1BD. The study included data on clinical-epidemiological features, immuno-hematological parameters, treatment, and outcome. Homozygosity mapping and haplotype analysis were used to evaluate the founder effect.

Results: We noted allergic/autoimmune and infective manifestations in all of our patients. Notable clinical features noted in our study include rheumatoid factor positive (RF+) chronic arthritis (mimicking RF+ juvenile idiopathic arthritis), significantly elevated anti-tissue transglutaminase antibody titers, generalized skin hyperpigmentation, distal phalangeal enlargement, frontal bone hypertrophy, hypertrophic skin scars, and hyperkeratosis. All cases harbored the founder splice-site variant c.64+2T>A in the ARPC1B gene. Long-term outcomes in our patients appeared worse than reported previously. Comparative phenotypic analysis showed significantly greater proportions of otitis, gastroenteritis, inflammatory bowel disease-like manifestations, and elevated IgA in patients with c.64+2T>A variant as compared to other variants. Homozygosity mapping (in eight probands) revealed that the gene/variant is contained within the only overlapping region of homozygosity (>1 Mb) across all autosomal chromosomes. Besides, the included probands share a similar haplotype around the said variant.

Conclusions: c.64+2T>A is a founder variant in Nepalese patients with ARPC1BD. This variant is associated with a severe clinical phenotype and diverse clinical complications.

Atopic dermatitis is the most prevalent chronic inflammatory skin disease, traditionally recognized for its defining eczematous lesions. However, the implications of atopic dermatitis extend far beyond eczema itself. Increasing understanding of the disease has enabled a more accurate characterization of its burden, including structural and functional skin alterations as well as various systemic comorbidities. This review examines the impact of the disease, beginning with the neuroimmune pathways underlying pruritus and its psychosocial burden, and progressing to the current concepts surrounding the atopic march and the broader spectrum of inflammatory or immune-mediated non-atopic comorbidities, including the emerging discussion on its similarities and differences with psoriasis. Special attention has been given to literature published from 2015 onwards. Ultimately, this review aims to deepen the understanding of the systemic nature of atopic dermatitis, providing a broader conceptual framework for assessing disease extent and severity.

Shellfish allergy, triggered by immune reactions to crustacean and mollusk proteins upon consumption/inhalation, is one of the most severe and persistent food allergies, affecting approximately 1%-3% of the general population worldwide. Shellfish is among the "big nine" food allergens responsible for over 90% of food allergy cases worldwide. Its diagnosis poses major challenges due to regional species diversity and a lack of reliable diagnostic tools. Management strategies generally emphasize strict avoidance and provision of emergency adrenaline autoinjectors; however, these approaches are inconvenient and insufficient for both patients and healthcare providers. Given the rising prevalence of shellfish allergy, there is an urgent need for targeted therapies that focus on key allergens, particularly tropomyosin-a major pan-allergen. As the primary target in current immunotherapy approaches, tropomyosin plays a central role in driving shellfish-induced immune responses. Recent advancements in immunotherapy are exploring alternatives beyond avoidance, aiming for long-term desensitization. This review discusses progress with allergen-specific immunotherapy, hypoallergenic allergen variants, DNA-based vaccines, and innovative approaches involving immunoregulatory peptides and probiotics. These strategies collectively strive to desensitize patients, reduce allergic symptoms, and enhance quality of life. Although some therapies are in active trials, most are in the investigational stages and offer promising directions for effective, patient-centered long-term management of shellfish allergy.

Primary Biliary Cholangitis is an autoimmune liver disease distinguished by Anti-mitochondrial Antibodies and chronic non-suppurative lymphocytic microcholangitis. UDCA remains the exclusively recommended initial therapy for PBC. However, 40% of patients experience either incomplete biochemical response or intolerance to UDCA, which represents poorer outcomes and increased mortality. Therefore, early identification of high-risk patients and timely intensive treatments are necessary to delay the progression of PBC and better improve the prognosis. Intensive therapeutic strategies based on more stringent treatment goals and early efficacy assessment criteria are elaborated in this review. To exclude AIH-PBC overlap syndrome, liver biopsy is required for cholestasis patients with negative AMAs or PBC patients who respond inadequately to UDCA, especially those with elevated ALT and IgG. Combined immunosuppressants are considered for patients with moderate-to-severe hepatitis. ALP normalization is considered the improved therapeutic goal for high-risk patients, which has been verified achievable in multiple treatment attempts. The control of pruritus and fatigue constitutes the key therapeutic targets in the symptom management of PBC. Bezafibrate, Seladelpar, and IBAT inhibitors have demonstrated significant therapeutic potential in pruritus. Last but not least, Liver Stiffness Measurement is substantiated as efficient in the fibrotic monitoring of PBC patients. OCA and fibrates are respectively useful for compensated and decompensated fibrotic patients. Moreover, the conventional efficacy assessment procedure, which is the "wait-to-fail" strategy, exhibits suboptimal sensitivity in the timely detection of treatment-responsive patients. Therefore, early prediction and evaluation criteria at baseline and 1-month treatment will help in timely interventions for patients with insufficient efficacy. This improved identification strategy is expected to provide precise and personalized treatment for PBC patients.