Clinical Reviews in Allergy & Immunology最新文献

Despite house dust mite (HDM)-allergy is the most frequent in the world, no standard questionnaire exists to help physicians in their clinical practice for screening patients with this possible diagnosis. The objective of this survey was to develop a questionnaire that could be used to identify patients with suspicion of HDM-allergy. The survey was conducted using the Delphi methodology. Nineteen international experts in allergology constituted the scientific board who established the items included in the first version of the questionnaire, defined the criteria of the selection for the next steps, and validated the final questionnaire and its interpretation. The initial version of the questionnaire included 15 items. For each item, five answers were suggested graduated by scores from "no importance" to "very high importance." The predefined conditions for the item selection after each round were a median score ≥ 7 and > 50% of responses according "high importance" and "very high importance." The electronic survey circulated within the Interasma Scientific Network platform. Eight questions based on the occurrence/worsening of symptoms induced by HDM-allergen exposure meet the survey criteria after the second and the third rounds and were included in the final questionnaire. Binomial answers for each question with 1 point accorded for "Yes" and none for "No" were suggested for the final version with a score ≥ 5 points associated with a high probability for HDM-allergy. By applying the Delphi process, we generated a brief questionnaire with binomial answers, easy to use in clinical practice for screening patients with HDM-allergy.

Asthma is a chronic respiratory disorder affecting individuals across all age groups. It is characterized by airway inflammation and remodeling and leads to progressive airflow restriction. While corticosteroids remain a mainstay therapy, their efficacy is limited in severe asthma due to genetic and epigenetic alterations, as well as elevated pro-inflammatory cytokines interleukin-4 (IL-4), interleukin-13 (IL-13), and interleukin-5 (IL-5), which drive structural airway changes including subepithelial fibrosis, smooth muscle hypertrophy, and goblet cell hyperplasia. This underscores the critical need for biologically targeted therapies. This review systematically examines the roles of IL-4 and IL-13, key drivers of type-2 inflammation, in airway remodeling and their potential as therapeutic targets. IL-4 orchestrates eosinophil recruitment, immunoglobulin class switching, and Th2 differentiation, whereas IL-13 directly modulates structural cells, including fibroblasts and epithelial cells, to promote mucus hypersecretion and extracellular matrix (ECM) deposition. Despite shared signaling pathways, IL-13 emerges as the dominant cytokine in remodeling processes including mucus hypersecretion, fibrosis and smooth muscle hypertrophy. While IL-4 primarily amplifies inflammatory cascades by driving IgE switching, promoting Th2 cell polarization that sustain cytokine release, and inducing chemokines to recruit eosinophils. In steroid-resistant severe asthma, biologics targeting IL-4/IL-13 show promise in reducing exacerbations and eosinophilic inflammation. However, their capacity to reverse established remodeling remains inconsistent, as clinical trials prioritize inflammatory biomarkers over long-term structural outcomes. This synthesis highlights critical gaps in understanding the durability of IL-4/IL-13 inhibition on airway structure and advocates for therapies combining biologics with remodeling-specific strategies. Through the integration of mechanistic insights and clinical evidence, this review emphasizes the need for long-term studies utilizing advanced imaging, histopathological techniques, and patient-reported outcomes to evaluate how IL-4/IL-13-targeted therapies alter airway remodeling and symptom burden, thereby informing more effective treatment approaches for severe, steroid-resistant asthma.

Inhalant allergen-mediated respiratory diseases, including asthma and allergic rhinitis, have become increasing global health issues. While air pollution is believed to favor allergic sensitization and intensify clinical symptoms of allergy, allergen sensitization can vary highly with geographical location, climate, and lifestyle differences. Pollen sensitization is higher in European countries, while dust mite is more common in regions with high humidity. Domestic pet sensitization is on the rising trend in industrialized nations, but the paradoxical effect of intensive cat exposure in early childhood is also observed. Clinical management of inhalant allergic diseases has greatly benefited from the immunological and mechanistic understanding of pathophysiology. In this review, we discuss the current knowledge on inhalant mediated allergic disorders with emphasis on (1) the major immune cells and relevant chemokines and cytokines in the sensitization and effector phase with aeroallergen exposure, (2) their manifestation in asthma and allergic rhinitis, (3) characterization of inhalant allergens, (4) chemical contributions to the development of allergic diseases, and (5) clinical diagnosis of aeroallergen sensitization and management of inhalant allergy. Knowledge on the role of Th2 skewing, IgE, basophil, mast cells, and eosinophils in respiratory allergic diseases are fundamental in the diagnosis and management of these disorders. Skin test, basophil activation test, and specific IgE component-resolved diagnostics are used for diagnosis and facilitate further management. Advances in the development of biologics and allergen-specific immunotherapy will strategize the future approaches in the clinical care of respiratory allergic diseases.

Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease characterized by chronic inflammation and multi-organ damage, influenced by genetic, environmental, and immunological factors. Recent research highlights the significant role of gut microbiota in the pathogenesis and progression of SLE, suggesting that dysbiosis-an imbalance in the microbial community-can contribute to disease onset and severity. The gut microbiota, through its metabolites, interacts with the host's immune system, influencing immune responses and maintaining intestinal barrier integrity. These interactions have positioned the gut microbiota as a potential source of diagnostic biomarkers and therapeutic targets for SLE. This review delves into the mechanisms by which gut microbiota influences SLE, exploring how alterations in microbial composition and function can trigger autoimmune responses. We also examine the potential of gut microbiota-derived metabolites as biomarkers for early diagnosis and disease progression monitoring. Additionally, the therapeutic implications of modulating gut microbiota through dietary interventions, probiotics, prebiotics, and other microbiota-targeted therapies are discussed as promising strategies for managing SLE. The findings suggest that a deeper understanding of the gut microbiota's role in SLE could lead to more personalized and effective treatments, potentially transforming the approach to managing this chronic autoimmune condition. Future research should focus on elucidating the precise mechanisms of gut microbiota interaction with the immune system and its impact on SLE, as well as validating gut microbiota-based biomarkers and therapies in clinical settings.

Idiopathic inflammatory myopathy (IIM) is a group of heterogeneous diseases that can affect multiple systems. Currently, it is classified into different subtypes based on myositis-specific antibodies and muscle tissue pathology. These subtypes vary in treatment response and clinical prognosis, with poor treatment outcomes observed in cases of rapidly progressive interstitial lung disease and severe muscle involvement. Despite conventional treatments, there remains a high rate of mortality and disability. The production of B cells and autoantibodies plays a crucial role in the pathogenesis of IIM. Targeting B cells has emerged as an effective therapeutic strategy for IIM. This review aims to summarize the current state of B cell-targeted therapies for IIM, providing clinicians with potential treatment options.

Osteoporosis, a common metabolic condition that affects the bones, increases the risk of fractures, thereby diminishing one's quality of life and, in severe cases, can even result in life-threatening conditions. Osteoporosis is becoming increasingly prevalent worldwide as the population ages. Previous research on osteoporosis has focused on skeletal cellular components such as osteoblasts and osteoclasts. The emerging field of "osteoimmunology" has recently been introduced through new research. The concept highlights the critical impact of bone-immune system interactions on osteoporosis progression. The pathogenesis of osteoporosis is significantly influenced by T cells, particularly cytotoxic and helper T cells, which modulate osteoclast differentiation and activity. A crucial aspect of understanding osteoporosis is how T lymphocytes interact with osteoclasts. However, the precise mechanisms underlying T cell-osteoclast crosstalk remain poorly understood. This review systematically examines T cell and osteoclast involvement in osteoimmunology, with a particular focus on their involvement in osteoporosis. It seeks to elucidate the immune mechanisms driving the progression of osteoporosis and identify key molecules involved in T cell-osteoclast interactions. This aims to discover novel molecular targets and intervention strategies to improve early diagnosis and management of osteoporosis. Furthermore, this article will explore the potential of intervening in T cell-osteoclast interactions using conventional therapies, traditional Chinese medicine, immunomodulatory agents, and nanomaterial-based treatments, providing new perspectives for future osteoporosis management.

Prurigo nodularis (PN) is a chronic, severely pruritic condition that markedly impairs quality of life. Existing treatments show limited efficacy, prompting investigation of nemolizumab, an IL-31 receptor antagonist. This meta-analysis evaluated randomized controlled trials (RCTs) comparing nemolizumab with placebo in patients with PN. Effectiveness endpoints included a ≥ 4-point improvement in the Peak Pruritus Numerical Rating Scale (PP-NRS4), a ≥ 2-point reduction in the Investigator's Global Assessment (IGA), and a ≥ 4-point improvement in the Sleep Disturbance Numerical Rating Scale (SD-NRS). Three RCTs involving 497 patients met the inclusion criteria. Pooled analyses showed nemolizumab significantly increased the likelihood of achieving PP-NRS4 response (OR = 6.92, 95% CI: 3.84-12.45, P < .00001), IGA reduction (OR = 7.59, 95% CI: 3.58-16.12, P < .00001), and SD-NRS improvement (OR = 3.99, 95% CI: 2.39-6.66, P < .00001). Safety outcomes did not differ significantly between nemolizumab and placebo for adverse events, serious adverse events, or other specific categories. In conclusion, while maintaining a favorable safety profile, nemolizumab demonstrates robust efficacy in reducing pruritus, lesion severity, and sleep disturbance in patients with PN. While these findings are promising, the small number of included studies and potential for publication bias warrant cautious interpretation and highlight the need for further research. These findings support its role as a promising option for individuals with PN who are unresponsive to standard therapies.

Vitiligo is an autoimmune depigmenting skin disorder and can affect the mental health of the patients. Current research suggests that the development of vitiligo involves a combination of genetic susceptibility, immune imbalance, and oxidative stress. However, its pathogenesis has not been fully elucidated. Epigenetic modification has gained increasing attention as an emerging way to regulate gene expression at the transcriptional or post-transcriptional level. Currently known modes of epigenetic modification include the regulation of non-coding RNAs, DNA methylation, and histone modification. Studies suggest they play important roles in tumors, immune disorders, and inflammatory diseases. In recent years, the value of epigenetics in the diagnosis, treatment, and prognosis of vitiligo has been explored. They showed the potential to serve as biomarkers and play a therapeutic role. In this review, we summarize the epigenetic modification mechanisms involved in the pathogenesis of vitiligo, including physiological processes such as immune homeostasis, melanocyte survival, cell adhesion and migration, and metabolism. This will help us fully understand the progress of epigenetic research in vitiligo and lay the foundation for targeted therapeutic-related research.

The prevalence of food allergy continues to rise, posing a significant burden on health and quality of life. Research on antigenic epitope identification and hypoallergenic agent design is advancing allergen-specific immunotherapy (AIT). This review focuses on food allergens from the perspective of molecular allergology, provides an overview of integration of bioinformatics and experimental validation for epitope identification, highlights hypoallergenic agents designed based on epitope information, and offers a valuable guidance to the application of hypoallergenic agents in AIT. With the development of molecular allergology, the characterization of the amino acid sequence and structure of the allergen at the molecular level facilitates T-/B-cell epitope identification. Alignment of the identified epitopes in food allergens revealed that the amino acid sequence of T-/B-cell epitopes barely overlapped, providing crucial data to design allergen molecules as a promising form for treating (FA) food allergy. Manipulating antigenic epitopes can reduce the allergenicity of allergens to obtain hypoallergenic agents, thereby minimizing the severe side effects associated with AIT. Currently, hypoallergenic agents are mainly developed through synthetic epitope peptides, genetic engineering, or food processing methods based on the identified epitope. New strategies such as DNA vaccines, signaling molecules coupling, and nanoparticles are emerging to improve efficiency. Although significant progress has been made in designing hypoallergenic agents for AIT, the challenge in clinical translation is to determine the appropriate dose and duration of treatment to induce long-term immune tolerance.

Lymph nodes (LNs) are ovoid-shape capsulated structures interposed along the lymphatic vessels. Owing to their unique architecture, LNs place immune cell types in distinct compartments allowing effective contact of antigens to them. Their efficient function results in the concentration of antigens and bridging of antigen-presenting cells like DCs and B cells and cells of adaptive immunity (circulating B and T lymphocytes remaining in LNs to monitor antigens) to coordinate efficient immune responses. In a healthy LN, B cells are primarily clustered in lymphoid follicles, whereas T cells are organized in the deeper paracortex region. Mast cells (MCs) are among the immune cells; their normal presence or pathologic infiltration has been reported in LNs. MCs enter LNs through afferent lymphatic vessels and can be found in all compartments, ranging from subcapsular sinus to the deepest sections of medullary sinus; however, they are commonly found in the T cell zone and medullary sinus but rarely in follicles. In pathologies with LN involvement and solid tumors, features like MC accumulation and the anatomical region of accumulation within LNs differ based on the type of tumor and the organ. Moreover, MC accumulation in LNs may influence the trafficking of other cell types and immune responses. MCs out of LNs can facilitate the migration of DCs into LN, which is crucial for orchestrating immune responses, especially in vaccination; moreover, MCs play a role in the induction of peripheral tolerance. MC-released mediators including TNF from tissue-resident MCs and tryptase from LN-MCs mediate hyperplasia and extension of LN vasculature, respectively. MCs support lymphangiogenesis by releasing VEGF-C and VEGF-D in vivo. Further research on the role of MCs in LNs is anticipated due to the development of pharmaceuticals that impact MC survival or inhibit their activation. In this review, we summarize the current literature regarding the outcomes of MC presence in LNs with a focus on the MC-mediated immune responses in two categories: direct cell-to-cell and mediator-based interactions.