Clinical Reviews in Allergy & Immunology最新文献

Immunodeficiencies in adults are increasingly recognized yet often remain underdiagnosed, leading to significant morbidity from recurrent infections, autoimmunity, and malignancy. Both primary immunodeficiencies (PIDs), now known as inborn errors of immunity (IEI), and secondary immunodeficiencies (SIDs) contribute to immune dysfunction in adults. Although SIDs are more common in adults due to factors like medications, malignancies, metabolic disorders, chronic conditions, and protein-losing conditions, IEI-particularly common variable immunodeficiency (CVID)-can also manifest in adulthood with diverse clinical features. Early recognition is crucial, with key warning signs including recurrent sinopulmonary infections, unexplained autoimmunity, poor vaccine responses, chronic diarrhea, bronchiectasis, and persistent lymphadenopathy. The diagnostic approach should be systematic. It begins with a detailed patient history and status followed by the evaluation of immunoglobulin levels, lymphocyte subsets, vaccine-specific antibody responses, and exclusion of secondary causes. Genetic testing, increasingly accessible, plays an important role in confirming the diagnosis of IEI and guiding prognosis and treatment. Management strategies focus on treating the underlying condition in SIDs. Preventive measures, including antimicrobial prophylaxis, vaccination, and immunoglobulin replacement therapy (IGRT) in patients with significant antibody deficiencies, are essential for reducing infections and complications in high-risk patients. Given the growing recognition of adult-onset immunodeficiency, clinicians should maintain a high index of suspicion and adopt a structured diagnostic and management approach to improve patient outcomes and quality of life.

PD-1 (Programmed cell death protein 1) located on T cells, binds to PD-L1 (Programmed cell death ligand 1) on cancer cells, to suppress T cell activation and enable immune evasion. Hitherto, reviews have mainly highlighted the role of PD-1/PD-L1 in anti-cancer immunomodulation, anti-cancer therapy resistance, and immune-related adverse events. However, there are critical modes of enhancement of therapeutic efficacy, which remain underappreciated. This review provides a holistic perspective on: (a) a comprehensive analysis of recent clinical trials targeting PD-1/PD-L1, specifically on the use of immune checkpoint inhibitors (ICIs); (b) the underlying molecular mechanisms of immune surveillance; (c) the role of ubiquitin-mediated post-translational modifications (PTMs, viz the ubiquitin machinery); and (d) the gut microbiome crosstalk with the PD-1/PD-L1 axis, which influences the tumor microenvironment (TME). Clarity gained from opinions exerted from these four factors, in this review, will provide insights on improving cancer prevention, diagnosis, and treatment, thus bridging translational research to the clinic. These standpoints will be presented with a view to advocating the integration of precision medicine with AI, to accelerate the discovery of more effective ICIs and enhance mono-/combinatorial drug strategies for PD-1/PD-L1-targeted therapy. Altogether, this review opines that AI-driven analytics will provoke an innovative impact on promoting clinical outcomes beneficial for cancer patients.

Glandular involvement of the head and neck is an extremely rare feature in ANCA-associated vasculitis (AAV). The objective was to describe glandular involvement in AAV by analysing data from a national cohort and comparing the findings to those from a systematic literature review. A multicentric retrospective study was conducted through a survey promoted by the French Vasculitis Study Group and included patients aged ≥ 16 years who met the ACR/EULAR classification criteria for AAV and had lachrymal and/or salivary involvement. Demographic, clinical and biological findings were analysed and pooled with data from a MEDLINE review of the literature since inception until June 5, 2024. The study population included 20 patients with a median age of 52 years (IQR, 44.5-57.5 years). Granulomatosis with polyangiitis (n = 17) and PR3-ANCA (n = 10) were the most represented. Parotitis (n = 9) and dacryoadenitis (n = 8) were found to precede and/or were present at AAV onset and recurrences. All patients received glucocorticoids, usually in combination with immunosuppressants. The systematic review identified another 67 cases. Pooled analysis of all cases (n = 87) showed that salivary gland involvement was not only frequently associated with ENT features (OR = 4.01 (95% CI, 1.30-13.06; p < 0.01)), but also with PR3-ANCA positivity (OR = 3.34 (95% CI, 1.09-11.34; p = 0.02)). Lachrymal involvement was associated with concomitant ophthalmological signs (OR = 3.93 (95% CI, 1.31-12.14; p < 0.01)). Glandular involvement of the head and neck is a rare but identifiable manifestation of active AAV. Knowledge of this uncommon presentation refines clinical assessment for optimal management of patients with AAV.

Food allergies affect 6-8% of children worldwide and can significantly impact quality of life, with potentially severe reactions including anaphylaxis. Over recent decades, oral immunotherapy (OIT) has emerged as a treatment option for food allergies, but safety concerns with conventional high-dose protocols have limited its broader adoption. Low-dose OIT protocols have been developed to address these safety issues while maintaining therapeutic efficacy. This review focuses specifically on low-dose OIT protocols, their clinical outcomes, and evidence-based patient selection strategies. Low-dose OIT has demonstrated efficacy for several food allergens via successful desensitization and sustained unresponsiveness (SU). Clinical trials have reported SU achievements of 33-50% for milk, up to 71% for eggs, 25-37.5% for wheat, and 33-74% for peanut allergies after treatment. Notably, these protocols have shown improved safety profiles compared to conventional higher dose approaches, with substantially reduced rates of severe adverse reactions. Long-term follow-up studies of up to 6 years have shown progressively improving SU rates and a decrease in adverse events over time, supporting the durability of low-dose approaches. Critical factors for successful low-dose OIT implementation include appropriate patient selection based on age, risk stratification, and individual clinical characteristics. Integration with biological agents such as omalizumab may further enhance safety and efficacy in selected high-risk patients. While low-dose OIT offers a safer therapeutic option for persistent food allergies, careful patient selection remains essential to optimize treatment outcomes and minimize risks.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently identified late-onset, X-linked autoinflammatory disorder caused by somatic mutations in the ubiquitin-like modifier activating enzyme 1 (UBA1) gene, which impair ubiquitination and protein degradation pathways. VEXAS is characterized by multisystem involvement, overlapping clinical features with other inflammatory conditions and high mortality. Despite growing attention, our understanding of its pathophysiology, immune dysregulation, and optimal treatments remains limited. This report aims to explore the molecular pathogenesis, diagnostic criteria, and therapeutic approaches for VEXAS syndrome in the context of chronic hepatitis B virus (HBV) infection. A 68-year-old Chinese male patient presented with persistent fever, fatigue, arthritis, weight loss, and hematologic abnormalities (severe macrocytic anemia and thrombocytopenia). Genetic testing revealed a somatic UBA1 mutation (p.Met41Val, c.121A > G, 67.84%) in myeloid cells, confirming VEXAS syndrome. The patient also had chronic HBV infection with active viral replication. Treatment included antiviral therapy (entecavir) for HBV and a combination of corticosteroids and immunosuppressants for VEXAS syndrome. After a follow-up of 6 months, significant improvements were observed in clinical symptoms, hematologic parameters, and inflammatory markers. This case highlights the interplay between chronic HBV infection and VEXAS syndrome-mediated immune dysregulation. Integrated antiviral and immunosuppressive strategies are essential to manage VEXAS syndrome with chronic hepatitis B virus comorbidity. Future studies should focus on targeted therapies, such as JAK-STAT inhibitors and IL-6 blockade, to improve outcomes in patients with chronic viral infections and VEXAS syndrome.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common upper airway inflammatory disorder, characterized by persistent inflammation of the sinonasal mucosa and nasal polyp formation. The pivotal roles of interleukin (IL)-4/IL-13 signaling in CRSwNP pathogenesis is increasingly recognized, evidenced by the remarkable clinical success of biologics targeting this pathway. This review provides a concise overview of the IL-4/IL-13 pathway in CRSwNP, encompassing its molecular architecture, pathogenic mechanisms, current targeted therapies, and emerging therapeutic strategies.

The ubiquitin-proteasome system (UPS) plays a crucial role in asthma by regulating protein stability And activity through post-translational modifications. This review provides a comprehensive Analysis of 42 UPS components in asthma, including one E2 ubiquitin-conjugating enzyme, 27 E3 ubiquitin ligases, eight deubiquitinating enzymes (DUBs), one dual-function (both E3 and DUB) enzyme, And five components of the 26S proteasome. Our Analysis focuses on four key pathological features, including airway inflammation, hyperresponsiveness, mucus hypersecretion, And remodeling. We identify 25 E3 ligase-substrate pairs and seven DUB-substrate pairs, detailing their ubiquitination and deubiquitination mechanisms. Additionally, a Literature review combined with GWAS data reveals 20 single-nucleotide polymorphisms (SNPs) across nine UPS Genes associated with asthma susceptibility. Therapeutic evaluations highlight 24 druggable UPS targets. Furthermore, we underscore 24 UPS-related compounds, with ten having established relevance to asthma And 14 exhibiting untapped potential. Emerging treatment strategies such as PROTACs and nanovaccines show promising potential. Overall, these findings provide new insights into UPS-mediated mechanisms and genetics in asthma and highlight its potential as a therapeutic target, paving the way for future research and clinical applications.

Allergic conjunctivitis (AC) is a common ophthalmic disease, ranging from mild, self-limiting forms to severe, vision-threatening conditions such as vernal keratoconjunctivitis and atopic keratoconjunctivitis. Its pathogenesis originates from the interplay between genetic predisposition and complex environmental factors, manifesting as a complex pathophysiological network. This review comprehensively elucidates recent advancements in the etiology and pathogenesis of AC. Key etiological drivers include Ig(Ig: Immunoglobulin) E-mediated reactions due to allergen sensitization, genetic susceptibility, and escalating environmental impacts, such as climate change, air pollution, and modern lifestyles influencing immune development and allergen exposure. Its pathogenesis is characterized by complex immune cell activation and crosstalk; dysregulation of lipid mediators; an intricate cytokine network predominantly driven by Th2(Th2: T helper 2) cytokines and alarmins that often signal via the JAK‒STAT(JAK‒STAT: Janus Kinase- Signal Transducer and Activator of Transcription) pathway; and a significant neuroimmune imbalance leading to neurogenic inflammation and persistent itch. Furthermore, epithelial barrier dysfunction, ocular surface microbiome dysbiosis, and epigenetic modifications are increasingly recognized as crucial regulatory factors. This review also highlights the ongoing challenges in addressing AC heterogeneity, pursuing personalized medicine, improving diagnostic methods, and developing effective preventive strategies, including allergen immunotherapy. Ultimately, integrating multidimensional data from cutting-edge research holds the promise of achieving more precise and personalized AC management, thereby improving outcomes for AC patients worldwide.

In the intricate regulation of gene expression, multiple regulatory elements play crucial roles. Among these, enhancers stand out as important elements that can boost the activity of promoters and make target genes more likely to be transcribed. Recent studies have revealed that sequence variations and gene rearrangements in enhancer regions could disrupt enhancer-promoter interactions, contributing to disease susceptibility and developmental abnormalities. Enhancer dysregulation is associated with numerous pathological conditions, spanning malignancies, autoimmune diseases, cardiovascular pathologies, and neurodegenerative ailments. Although the advent of high-throughput sequencing has enabled comprehensive enhancer profiling across the genome, elucidating their precise functional mechanisms continues to pose significant challenges. This review summarizes the structural features, identification methodologies, transcriptional regulatory mechanisms, and pathogenic contributions of enhancers in autoimmune diseases. Furthermore, we highlight emerging enhancer-based therapeutic strategies, offering novel insights for the targeted treatment of immune-related disorders. Additionally, we explore the role of phase separation in enhancer regulation and its potential association with autoimmune pathogenesis, proposing phase separation modulation as a promising therapeutic avenue.

Islet macrophages are considered to be irreplaceable in maintaining the immune microenvironment homeostasis. The M1/M2 imbalance can trigger the initiation of islet autoimmunity and persists throughout the entire process of type 1 diabetes. The identification of macrophage transcriptional clusters and phenotypes by single-cell sequencing has facilitated in-depth studies on the role of macrophages in the pathogenesis of type 1 diabetes. Macrophages exert extensive endocrine and paracrine effects on the islets by secreting various bioactive chemicals, especially exosomes, which facilitate cell-cell communication. Resident islet macrophages directly influence the biological properties of islet tissue. Meanwhile, the interaction between macrophages and islet cells is bidirectional. Cell-cell interactions also closely govern the polarization and activity of macrophages. An imbalance in the transition from M2 to M1 macrophages may lead to inflammation and islet dysfunction. Here, we have discussed the latest research progress on macrophages in the islet immune microenvironment homeostasis, the mechanisms of interactions between macrophages and islet cells in type 1 diabetes, and analyzed the possible clinical consequences. Furthermore, we highlighted emerging technologies for non-invasive detection of macrophages and summarized how therapeutic targeting of macrophages may be beneficial for patients with type 1 diabetes.