Clinical Reviews in Allergy & Immunology最新文献

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.

Kawasaki disease (KD) is an acute, self-limiting systemic vasculitis of early childhood and remains the leading cause of acquired heart disease in developed nations. Despite decades of investigation, its etiology and immunopathogenesis are still not fully understood. This review integrates nearly six decades of histopathological, epidemiological, and immunological research to examine infection-driven mechanisms underlying KD. Current evidence indicates that KD may result from a convergence of microbial and host factors: viral infections can trigger mucosal IgA-mediated immune activation; superantigens may induce T-cell receptor (TCR) Vβ-skewed cytokine release; conventional antigens appear to elicit oligoclonal adaptive immune responses consistent with infection-associated vasculitis; and gut microbiota dysbiosis may amplify systemic inflammation through disruption of intestinal barrier integrity and short-chain fatty acid metabolism. Rather than a single-pathogen infection, KD likely reflects infection-triggered immune dysregulation in genetically susceptible children. By contrasting these mechanistic hypotheses, this review highlights the need for longitudinal, multi-omics studies integrating metagenomic, transcriptomic, and serologic analyses to delineate causal microbial signatures, identify diagnostic biomarkers, and guide precision immunomodulatory strategies for this complex pediatric vasculitis.

Mpox, formerly known as monkeypox, has recently spread beyond its traditional epidemic areas. Several regions of Africa have been affected and have become a health concern globally. This review presents epidemiology, clinical symptoms, diagnostic developments, treatment methods, and policy gaps of Mpox. Methodologically, this review incorporates data from over 70 peer-reviewed journal articles, official epidemiological bulletins, and curated surveillance datasets from WHO, CDC, and PubMed to provide an evidence-based analysis of Mpox. As all data were derived from secondary sources, no sampling method was utilized. Firstly, we examined the primary causes of the virus's resurgence, including zoonotic spillover, human-to-human transmission, and globalization, which contribute to the spread of Mpox disease. Next, we discussed different treatment alternatives for Mpox, such as Tecovirimat and JYNNEOS vaccination, diagnostic techniques including polymerase chain reaction (PCR), serological tests, and new point-of-care diagnostics based on clustered regularly interspaced short palindromic repeats (CRISPR). Then, we highlighted the public health challenges of Mpox, including misdiagnosis, healthcare disparities, and the impact on immunosuppressed populations, particularly HIV-positive individuals. Finally, this study discussed the socioeconomic implications of Mpox outbreaks, emphasizing the need for global collaboration, enhanced surveillance, and robust vaccination programs to minimize future outbreaks.

The skin is a highly innervated and immunologically active barrier organ, where neuro-immune interactions critically shape both physiological homeostasis and disease progression. Growing evidence indicates that bidirectional crosstalk between the nervous and immune systems is not only central to the pathogenesis of allergic skin diseases but also represents an emerging frontier for therapeutic innovation. In this review, we systematically examine atopic dermatitis (AD), contact dermatitis (CD), and urticaria, integrating insights into peripheral pathways-mediated by sensory neurons, cytokine networks, and immune cells-and central mechanisms involving the hypothalamic-pituitary-adrenal axis and higher neural circuits. By contrasting shared and disease-specific neuro-immune signatures, we highlight how these mechanisms underlie distinct inflammatory phenotypes and clinical manifestations. We further evaluate current and investigational therapies, including biologics and small molecules that target neuro-immune signaling, and discuss their translational significance. Looking ahead, we identify unresolved questions and propose future directions aimed at leveraging neuro-immune mechanisms to advance precision diagnosis and personalized interventions in allergic skin diseases.

Secondary antibody deficiency (SAD) represents a substantial yet under-recognised global healthcare burden. It is more prevalent than primary antibody deficiency, but frequently under-diagnosed and variably managed worldwide. Prompt diagnosis is often hindered by insufficient awareness among clinicians, lack of global consensus on screening/monitoring for SAD among at-risk patients, inadequate clinical immunology services and lack of standardised referral pathways/protocols. Management practices vary widely, with little international agreement, particularly regarding threshold to initiate immunoglobulin replacement, as well as regimen, dosage and frequency of immunoglobulin administration. Subcutaneous immunoglobulin (SCIg) replacement emerged as a promising alternative to traditional intravenous immunoglobulin (IVIg) replacement. IVIg requires monthly infusions in inpatient/day-hospital settings leading to high peak serum IgG and subsequent variations with end-of-cycle 'wear-off effect', causing more systemic side effects and increased risk of breakthrough infections, and disruption of daily life and employment. While previous evidence was largely derived from primary antibody deficiency, recent comparative studies on SAD patients indicate that SCIg replacement, through weekly self-administered infusions, can achieve more stable and higher trough serum IgG, lower infection rates, fewer systemic adverse reactions and enhanced health-related quality-of-life compared to IVIg. There is also potential cost-savings from the use of SCIg replacement. This review emphasises the urgent need for standardised guidelines on screening/diagnosis and treatment of SAD, and large-scale multi-centre trials and real-world studies on IVIg vs SCIg replacement among SAD patients, which will facilitate better identification, management, and health-outcomes for SAD patients, ultimately alleviating a significant global health challenge through coordinated clinical, research, and policy efforts.

Common Variable Immunodeficiency Disorders (CVID) are the most frequent symptomatic Primary Immunodeficiency (PID) in adults and children. Patients with CVID present with predominant antibody deficiency with varying degrees of impaired cellular immunity. CVID was previously a diagnosis of exclusion, which led to considerable uncertainty about which patients would qualify for subcutaneous or intravenous immunoglobulin (SCIG/IVIG) replacement. Over the last twelve years, several sets of diagnostic criteria have been published which identify these disorders with greater precision. These new CVID diagnostic criteria assist with decisions on treatment, particularly SCIG/IVIG replacement. With the advent of massively parallel genome sequencing technologies, it has become apparent that a significant proportion of individuals with a CVID phenotype have an underlying causative genetic defect. If such a pathogenic variant is identified, these individuals are removed from the overarching diagnosis of CVID and are deemed to have a CVID-like disorder caused by a specific Inborn Error of Immunity (IEI). New Zealand has had a long-standing customized PID genetic testing program. Two novel autosomal dominant pathogenic variants causing CVID-like disorders, consequent to haploinsufficiency of Nuclear Factor kappa-light-chain-enhancer of activated B cells (NFKB1) and Transcription Factor 3 (TCF3), were identified in New Zealand families. The latter pathogenic variant was shown to have an epistatic interaction with TNFRSF13B (TACI) in a patient with a digenic CVID-like disorder. Epistasis is the synergistic, non-linear interaction between two or more genetic loci, leading to much more severe (or much milder) disease. This perspective reviews the current understanding of these disorders with contributions from three New Zealand-based studies: The Prospective NZ CVID and the NZ hypogammaglobulinemia sub-studies as well as a large retrospective case series of Transient Hypogammaglobulinemia of Infancy (THI). These clinical and genomic studies have offered insights into the complexities of these rare PIDs. This review examines current areas of uncertainty in the diagnosis of of these disorders.

We are living in an era where food allergy is increasingly prevalent, and shrimp allergy (SA) is among the most common and potentially severe reactions worldwide. Significant efforts have been made to improve diagnostic accuracy and treatment options. However, diagnosing SA remains challenging due to its diverse clinical presentations and the complexity of shrimp allergens. The pathogenesis of SA is complicated by various allergens sensitization, epithelial barrier disruption and gut microbiota dysbiosis. To date, at least ten shrimp allergens have been identified, but sensitization profiles vary significantly across populations. Promising novel immunotherapy approaches have been explored, showing potential in murine models. The use of physiologically relevant experimental systems, from in vivo models (e.g., murine studies) to advanced ex vivo human-based techniques (including organoids, organ-on-a-chip platforms, and tissue slice cultures), offers promising alternative for studying biological processes that are difficult to investigate directly in humans. These models have emerged as a valuable tool in food allergy research by providing critical insights into food-gut interactions, gut microbiota-host dynamics epithelial barrier integrity and cross-talk between epithelia and immune cells, and signaling and inflammatory markers. This review aims to summarize recent advancements in the diagnosis and treatment of SA, and the potential in vivo/ex-vivo models in SA research.

Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disorder characterized by loss of self-tolerance, immune complex deposition, and progressive organ damage. Despite advances in immunosuppressive therapy, a subset of patients develops treatment-resistant or refractory manifestations; terms used variably in the literature to describe inadequate response to multiple standard immunosuppressants. Chimeric antigen receptor T cell (CAR-T) therapy, a revolutionary modality in oncology, is now emerging as a promising approach in severe autoimmune diseases including SLE. By redirecting autologous T cells to target B cell antigens such as CD19 or BCMA, CAR-T therapy enables deep and sustained B cell depletion, potentially resetting immune tolerance.Early case series have reported encouraging remission rates and serologic improvements in refractory SLE; however, these observations derive from small, uncontrolled studies. The long-term durability, relapse risk, safety profile, and cost-effectiveness of CAR-T therapy in autoimmune disease remain uncertain and require confirmation in larger, controlled trials. This narrative review synthesizes the current understanding of CAR-T therapy in SLE, covering immunopathogenesis, rationale for B cell targeting, CAR-T mechanisms, preclinical evidence, clinical outcomes, safety considerations, and future directions. We integrate data from peer-reviewed studies, conference abstracts, and preprints up to August 2025, and propose a framework for integrating CAR-T into the treatment paradigm for refractory SLE.

Atopic dermatitis (AD), characterized by skin barrier dysfunction and microbiota dysbiosis, is closely linked to immune microenvironment imbalance. Growing evidence highlights the crucial role of microorganisms and their metabolites in immune regulation. Understanding their molecular mechanisms in AD, combined with precision nutrition-driven personalized network analysis, will accelerate innovative intervention strategies. This review summarizes these regulatory mechanisms and current research progress, outlining applications, challenges, and limitations for key targets, such as the TSLP-ILC2-IL-13 axis, IL-31-TRP channels, and SCFA-GPR43 signaling. The precision nutrition-driven approach will leverage multi-omics data, including metagenomics, metabolomics, and host transcriptomics, with integration techniques such as network analysis and machine learning to explore the spatio-temporal regulation of the immune microenvironment. Beyond immunomodulation, dietary factors significantly impact AD progression. We propose "precision nutrition" strategies to mitigate AD risk and burden, including microbiota-targeted dietary patterns, personalized probiotics, and delivery systems for "precise skin nutrition." Synergizing traditional interventions with localized innovations and interdisciplinary tools is expected to enable precise, spatio-temporal immune regulation. This enhances understanding of microorganism-metabolite, precision nutrition, and immune microenvironment connections, advancing AD intervention and treatment.

Chimeric Antigen Receptor (CAR) T cell therapy has revolutionised the treatment of relapsed/refractory B cell leukaemia, lymphoma and multiple myeloma through targeting of CD19 and BCMA antigens on the surface of these cells. A growing body of evidence has recently demonstrated that these cell-based therapies can also target autoimmune diseases including systemic lupus erythematosus, systemic sclerosis, neuromyelitis optica spectrum disorder, myasthenia gravis, idiopathic inflammatory myositis, multiple sclerosis and rheumatoid arthritis. To date, ten patients with rheumatoid arthritis have been treated with CAR T cells targeting CD19/CD20 or BCMA antigens on B cells. Nine patients with seropositive disease have shown remarkable responses, including depletion of circulating B cells, ablation of autoantibody levels and drug-free remission. A tenth patient with seronegative disease initially responded to CAR T cell therapy but later relapsed. This review provides in-depth analysis of these single case studies and highlights emerging in-vitro and animal model studies where T cell subsets have been engineered with CARs to fine-tune their immune responses for the treatment of rheumatoid arthritis, including targeting of autoreactive B cells, autoreactive T cells or fibroblasts. CAR T cell therapy holds enormous promise for the treatment of difficult-to-treat rheumatoid arthritis, but more research and large clinical trials are needed to confirm its efficacy and safety.