Clinical Reviews in Allergy & Immunology最新文献

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.

Self-DNA sensing by the immune system was discovered more than half a century ago. It has emerged as a key factor in the development of cancer, autoimmune diseases and many inflammatory diseases. While the innate immune response has been extensively studied, how self-DNA drives adaptive immune responses, particularly those mediated by T cells, has only been gradually unraveled over the past decade. In fact, adaptive DNA immunity plays a role in key cellular activities relevant to physiology and disease, containing cell functional activation, proliferation, differentiation, senescence and apoptosis. Herein, we review the latest research of self-DNA induced T cell immune response from the point of the origin of self-DNA, the mechanism of T cell responses to self-DNA and the fate of T cells. We also summarize how these cellular maneuvers influence disease outcome in mammalian cells, providing an overview of the expanding landscape of self-DNA-evoked T cell immunity.

The emergence of SARS-CoV-2 has not only reshaped our understanding of viral pathogenesis but also highlighted its capacity to trigger autoimmune and inflammatory diseases. Accumulating evidence indicates that SARS-CoV-2 infection can lead to a broad spectrum of immune-mediated complications, ranging from well-defined conditions such as Guillain-Barré syndrome, multisystem inflammatory syndrome in children (MIS-C), and systemic lupus erythematosus, to the development of diverse autoantibodies and atypical inflammatory phenotypes. This review synthesizes the current clinical and experimental evidence linking COVID-19 to autoimmune and inflammatory sequelae. We have provided a structured overview on the multifactorial mechanisms underpinning this immune dysregulation, including molecular mimicry, epitope spreading, bystander activation, cytokine storm, host genetic predisposition, and viral genomic variability. Additionally, we discussed the contribution of gut dysbiosis and metabolic reprogramming in shaping aberrant immune responses following infection. Special attention is given to the therapeutic potential of intravenous immunoglobulin (IVIG), which has shown promise in mitigating hyperinflammation and modulating autoimmunity in affected individuals. IVIG can provide therapeutic benefits by diverse mutually nonexclusive mechanisms. By integrating emerging insights across clinical immunology, virology, and host-pathogen interactions, this review aims to advance our understanding of COVID-19-induced immune complications and therapeutic strategies to manage post-COVID autoimmune and inflammatory syndromes.

Myopia represents a growing global public health challenge, characterized by increasing prevalence and associated complications such as myopic macular degeneration and retinal detachment. Although genetic and environmental factors are well-recognized contributors, emerging evidence supports a pathological link between inflammation and myopia progression. Epidemiological studies indicate a higher incidence of myopia among individuals with systemic or ocular inflammatory conditions. Inflammation perturbs the ocular immune microenvironment by upregulating pro-inflammatory cytokines and matrix metalloproteinase-2, thereby accelerating extracellular matrix (ECM) degradation and scleral remodeling, which culminates in axial elongation. Conversely, excessive axial elongation in high myopia triggers choroidal microvascular dysfunction, tissue hypoxia, and disruption of the blood-retinal barrier, leading to elevated inflammatory cytokines in the aqueous humor and vitreous, thereby raising the possibility of a self-perpetuating loop. Anti-inflammatory agents, including diacerein, resveratrol, and lactoferrin, have demonstrated therapeutic potential in experimental models by modulating inflammatory pathways, reducing pro-inflammatory cytokines, and preserving ECM integrity. However, their clinical efficacy and long-term safety require further validation. Elucidating the complex interplay between inflammation and myopia is pivotal for the development of targeted interventions, moving the focus of myopia management beyond optical correction towards disease-modifying strategies.

In recent years, the prevalence of obesity and asthma has risen steadily, emerging as two major chronic diseases threatening public health. These conditions exert mutual promotion and may induce pathological superposition effects in obesity-related asthma. Obesity-related asthma represents a distinct asthma phenotype, with pathogenesis involving chronic low-grade inflammation, metabolic dysregulation, mechanical constraints, and genetic predispositions. Critically, four core components, including adipose dysfunction with metabolic dysregulation, gut microbiota dysbiosis with intestinal barrier impairment, systemic chronic inflammation, and pulmonary inflammation with airway hyperresponsiveness, interlock into a self-reinforcing cycle that synergistically amplifies disease progression. Accordingly, obesity-related asthma exhibits a greater clinical burden than classical asthma, including more severe symptoms, higher exacerbation rates, and poorer therapeutic responsiveness. As key metabolites derived from gut microbiota, short-chain fatty acids (SCFAs) demonstrate potential to disrupt this pathological cycle in obesity-related asthma through anti-inflammatory actions, immune-metabolic modulation, and epithelial barrier protection. Furthermore, SCFA levels can be effectively modulated through dietary interventions, microbial preparation supplementation, and fecal microbiota transplantation, positioning them as promising translational targets for obesity-related asthma.

ETS1 and FLI1 exhibit distinct roles in immunoregulation and autoimmune pathogenesis. Previous transethnic genome-wide meta-analyses incorporating our Han Chinese population established significant associations between ETS1 single-nucleotide polymorphisms (SNPs) and susceptibility to primary biliary cholangitis (PBC). In our earlier genome-wide association study (GWAS), ten SNPs within the ETS1 and FLI1 loci demonstrated modest yet suggestive associations with PBC susceptibility in the Han Chinese population. To validate these putative risk loci, we conducted an independent replication study of rs10893900 and rs2246290 using a separate Han Chinese PBC cohort. A meta-analysis combining data from two stages identified rs10893900 as a genome-wide significant variant (P = 4.55 × 10^-8, OR = 1.19, 95% CI = 1.12-1.27). Subsequent functional characterization identified rs10893900 as a susceptibility-associated functional variant. Based on the literature review, we summarized ETS1 variants' susceptibility to human autoimmune diseases, including SLE, RA, and PBC, and evaluated these variants in silico analysis. Importantly, our research implicates the importance of ETS1 involving JAK-STAT signaling pathway, expanding the understanding of pathological mechanisms of PBC.