Expert Review of Clinical Immunology最新文献

Introduction: Obstetric antiphospholipid syndrome (OAPS) is a complex autoimmune disorder that contributes significantly to pregnancy morbidity. Despite advances in understanding its mechanisms, 20-30% of women, especially those refractory to standard treatments, continue to face adverse outcomes. Emerging therapies, including biologics and immunomodulators, are under investigation; however, data in this field remain limited.

Areas covered: This review examines the current understanding of OAPS pathogenesis and risk stratification. It evaluates established management strategies such as aspirin and heparin, and explores adjunctive or investigational therapies, including hydroxychloroquine, corticosteroids, intravenous immunoglobulins, statins, plasma exchange, and biologics. Key knowledge gaps, concerning refractory cases and personalized treatment approaches, are highlighted, emphasizing the importance of multidisciplinary, risk-based care throughout preconception, pregnancy, and postpartum. This review focuses primarily on primary OAPS rather than secondary APS associated with systemic lupus erythematosus.

Expert opinion: Innovations in immunotherapy and targeted biologics hold promise for refractory OAPS; however, large trials are needed to confirm their safety and efficacy during pregnancy. Future management is likely to involve biomarker-driven strategies, incorporating machine learning to enhance prediction and individualization of treatment. The development of standardized diagnostic criteria and risk assessment tools, alongside multidisciplinary collaboration, will be crucial in advancing care, ultimately transforming maternal-fetal health outcomes.

Introduction: Interleukin-15 (IL-15) is a pleiotropic, pro-inflammatory cytokine, constitutively expressed in both hematopoietic and non-hematopoietic cells. The role of IL-15 during systemic inflammatory diseases, including autoimmune and autoinflammatory disorders, is to be fully clarified yet. Due to its effects on immune cells, IL-15 has attracted attention as a potential new therapeutic target for modulating immune responses, either by enhancing immune surveillance or by controlling excessive inflammation.

Areas covered: We provided a landscape about IL-15 in systemic inflammatory diseases, from its biological functions to the possible mechanistic roles, using rheumatoid arthritis (RA) and Still's disease as autoimmune and autoinflammatory models, respectively.

Expert opinion: IL-15 exerts its pathogenetic activity by the induction of a deregulated activation of innate and adaptive arms of the immune system, at the crossroad of autoimmune and autoinflammatory disorders. During RA, IL-15 mediates the production from T cells and macrophages of TNF, which may induce further production of IL-15 by synoviocytes via a vicious pathogenic loop. During Still's disease, together with IFN-I, IL-15 promotes the expansion of NK cells and of CD38+HLA-DR+ T cells, which are highly activated in disease life-threatening evolution. Thus, novel IL-15-targeted therapeutic strategies could be explored to improve the management of systemic inflammatory diseases.

Introduction: The intratumor microbiome is a key component of the tumor microenvironment, influencing oncogenesis, immune modulation, and therapeutic responses. Bacteria, fungi, and viruses infiltrate tumor tissues, modulating local immunity and potentially conditioning the efficacy of immune checkpoint inhibitors. While mucosal-origin tumors exhibit an expected microbial presence, sterile organ tumors, such as brain and breast, reveal less intuitive microbial infiltration.

Areas covered: This review evaluated the interplay between the intratumoral microbiota and the immune system across different stages of carcinogenesis, including initiation, progression, and metastasis. Sources included PubMed, Embase, and Google Scholar; searches covered December 2024 to October 2025. We examine microbial metabolites, immune hijacking, and routes of dissemination. We also overview technologies for tumor microbiome characterization, including next-generation sequencing, spatial transcriptomics, and artificial intelligence (AI), with machine learning and deep learning, to support diagnostics, prediction of treatment response, and personalized oncology.

Expert opinion: Defining the spatial localization and functions of intratumoral microorganisms is crucial for robust biomarkers and tailored interventions. Integrating AI with spatial and multi-omics data offers major opportunities but faces obstacles - data heterogeneity, model interpretability, and ethical issues. Priorities include standardized protocols, high-resolution spatial profiling, external validation, and expertly annotated datasets to unlock microbiome-informed precision oncology.

Introduction: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) has become standard treatment for patients with melanoma after the publication of a phase III trial showing an improvement of progression-free survival of metastatic melanoma patients treated with TIL-ACT compared to patients treated with the immune checkpoint inhibitor ipilimumab. Recent clinical trials also tested TIL-ACT in patients with other immunogenic cancers including non-small cell lung cancer or cervical carcinomas.

Areas covered: Some factors were associated with long-term response to TIL-ACT including the number of cells applied to the patient or ratios of CD8⁺ versus CD4⁺ T cells. Here, we summarize known factors that are associated with response or resistance to TIL-ACT. We also give an outlook, which factors could be improved to overcome resistance and to enhance long-term outcome of patients.

Expert opinion: TIL-ACT shows promise beyond niche use, but its success depends on overcoming resistance driven by patient, tumor, and product factors. Advancing its efficacy will require refined patient selection, TIL optimization, and mechanistic insights to inform new, improved treatment approaches.

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by diastolic dysfunction, systemic comorbidities, and chronic low-grade inflammation. Emerging evidence suggests that immune dysregulation plays a central role in its pathophysiology. Both innate and adaptive immune responses contribute to myocardial remodeling, endothelial dysfunction, and comorbidity-driven inflammation that are hallmarks of HFpEF.

Areas covered: In this systematic review, we summarize current evidence on the contribution of immunological pathways to HFpEF, including the role of proinflammatory cytokines, immune cell infiltration (particularly macrophages, mast cells, and T cells), and immune - endothelial interactions. We also highlight findings from experimental models linking systemic metabolic inflammation to myocardial fibrosis, coronary microvascular dysfunction, and cardiomyocyte stiffness in HFpEF. Finally, we explore potential immunomodulatory therapeutic approaches currently under investigation and discuss biomarkers of immune activation with potential clinical relevance.

Expert opinion: While no immunologically targeted therapy is yet approved for HFpEF, interventions that modulate inflammation - such as IL-1 blockade, mast cell stabilization, or myeloid-targeted therapies - offer promise. Future clinical trials should incorporate immune profiling to enable patient stratification and personalized treatment approaches. A deeper understanding of immune-mediated mechanisms in HFpEF will be essential to advance therapeutic innovation and improve outcomes in this challenging and growing patient population.

Introduction: Up to 30% of patients with psoriasis develop psoriatic arthritis (PsA) during their lifetime, which can result in irreversible joint damage. Early identification and interception of PsA could potentially decrease inflammation and progression of structural damage. This review summarizes the state of the art on psoriasis-to-PsA transition and discusses the challenges to prevent and early manage PsA.

Areas covered: One primary hurdle clinicians face is their inability to establish an early PsA diagnosis because of the poor specificity of symptoms. Arthralgia, severe psoriasis, a history of uveitis, nail psoriasis, scalp psoriasis, having a first-degree relative with PsA, familial aggregation, genetic factors, specific skin phenotypes, mechanical stress, and obesity confer an increased risk of PsA transition. However, underlying molecular and cellular mechanisms remain poorly defined.

Expert opinion: The evolution from cutaneous to synovio-entheseal inflammation in patients with psoriasis presents an opportunity to investigate the critical events linked to arthritis development. Further efforts should be made to clearly define early PsA and identify patients with psoriasis at increased PsA risk. Machine learning and artificial intelligence may analyze and integrate different factors to more objectively estimate the possible risk of psoriasis to PsA transition for each patient.

Introduction: Rhupus syndrome refers to the coexistence of clinical, serological, and imaging features characteristic of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Although recognized for decades, its natural history, immunopathogenesis, and optimal management remain incompletely defined.

Areas covered: This narrative review (PICo framework) outlines the historical evolution and current understanding (from inception to 2025) of rhupus, emphasizing its hybrid phenotype: dual autoantibody profiles including rheumatoid factor, anti-citrullinated and anticarbamylated protein antibodies, and antinuclear and extractable nuclear antigen antibodies; RA-like erosive arthropathy demonstrable by radiography, ultrasound, and magnetic resonance imaging; and a variable, frequently milder spectrum of SLE involvement. Genetic studies implicate shared autoimmune susceptibility loci, most notably HLA-DRB1 shared-epitope alleles and PTPN22, while immunophenotyping reveals enrichment of T-helper 1 (Th1)-polarized and CD4⁺ CD28^null T-cell expansion alongside B-cell hyperactivity. Evidence guiding treatment is largely observational; nonetheless, conventional disease-modifying antirheumatic drugs, B-cell depletion, abatacept, and selective use of targeted synthetic agents have demonstrated benefit in subsets of patients.

Expert opinion: Progress in rhupus requires standardized classification criteria, prospective international registries, and longitudinal multi-omic and single-cell analyses integrated with advanced imaging. A coordinated research agenda is essential to transition rhupus from a poorly defined clinical overlap to a precision-managed autoimmune entity.

Introduction: Drug provocation tests (DPT) are considered the gold standard for diagnosing drug hypersensitivity reactions (DHRs) and can provide diagnostic clarity when other tests are limited. However, their use remains controversial due to safety concerns and lack of standardized test protocols.

Areas covered: Drawing upon literature published by major allergy societies and recent studies, this review explores the current controversies surrounding DPTs, including their use in patients with severe index reactions, potential risks, and challenges related to test protocol variability and result interpretation. Special considerations in vulnerable populations such as pregnant women and those with limited therapeutic options, and clinically important drugs, such as penicillin's and nonsteroid anti-inflammatory drugs (NSAID), are also discussed. Despite the controversies, reliance on DPTs is increasing and are invaluable in the evaluation of DHRs. Nonetheless, the application of DPTs must be guided by careful patient selection, individualized risk stratification and thorough risk-benefit assessment, especially in complex scenarios.

Expert opinion: More collaborative studies are needed to enhance safety evaluation and develop reliable, standardized protocols to address current inconsistencies and improve clinical outcomes. A combination of improved testing algorithms will be key to maximize the potential of DPTs, optimize outcomes and improve patient care.