Expert Review of Clinical Immunology最新文献

Introduction: Autoinflammatory diseases are inherited disorders of innate immunity, broadly classified into inflammasomopathies, interferonopathies, and complement-mediated disorders. They are characterized by dysregulated cytokine signaling - particularly IL-1, IL-6, TNF, type I interferon, and the JAK-STAT pathway-and are increasingly managed with molecular targeted therapies. Prototypical entities include familial Mediterranean fever (FMF), TNF receptor - associated periodic syndrome (TRAPS), and cryopyrin-associated periodic syndromes (CAPS). Other conditions - notably mevalonate kinase deficiency (MKD/HIDS), deficiency of adenosine deaminase 2 (DADA2), haploinsufficiency of A20 (HA20), OTULIN-related autoinflammatory syndromes, and proteasome-associated autoinflammatory syndromes (PRAAS) - are now recognized as biologic-responsive diseases.

Areas covered: This review summarizes molecular mechanisms and therapeutic strategies, focusing on IL-1 blockade with anakinra, canakinumab, and rilonacept, as well as IL-6 and TNF inhibitors, integrating evidence from clinical trials and real-world studies.

Expert opinion: IL-1 inhibition has transformed the management of inflammasome-mediated diseases, enabling glucocorticoid-free remission and reducing amyloidosis risk. TNF inhibitors remain standard for vasculopathic disorders such as DADA2, while IL-6 blockade and JAK inhibitors are options in selected refractory cases. The recognition of novel syndromes, including HA20, OTULIN deficiency, and PRAAS, has broadened the therapeutic landscape, and next-generation biologics may further enable personalized treatment.

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality worldwide, with type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease being common co-morbidities associated with worse outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors, which were originally developed for treatment of T2DM and/or obesity, have recently been shown to reduce exacerbations in observational studies of patients with COPD, suggesting that repurposing GLP-1RAs and SGLT2 inhibitors could improve clinical outcomes in COPD.

Areas covered: COPD, diabetes, and obesity share several common inflammatory pathways, including macrophage dysfunction, inflammasome activation, and metabolic dysregulation. Here we review the pharmacology, pre-clinical, and emerging clinical data which could support repurposing of GLP-1RAs and SGLT2 inhibitors for use in COPD through a search of articles in PubMed and Medline from 01/1950 to 08/2025.

Expert opinion: Reevaluating metabolic therapeutic targets has the potential to redefine treatment strategies for patients with COPD and metabolic comorbidities. Potential mechanisms of action could be via modulation of the NLRP3 inflammasome and macrophage polarization or better control of co-morbid conditions. However, randomized controlled trials and mechanistic studies are needed to confirm these observational findings and elucidate underlying mechanisms.

Introduction: This meta-analysis evaluates the risk of all-cause and cause-specific mortality in patients with atopic dermatitis (AD).

Methods: A systematic search of PubMed, EMBASE, and the Cochrane Library (from inception to April 2025) was conducted for cohort studies comparing mortality risks in AD patients versus controls, in accordance with PRISMA guidelines. Two reviewers screened studies, extracted data, and assessed quality using the Newcastle-Ottawa Scale. Hazard ratios (HRs) were calculated using random-effects models in Stata 14.0, with sensitivity analyses, subgroup analyses, and publication bias assessments.

Results: Nine cohort studies were included. AD patients had significantly increased risks of all-cause mortality [HR = 1.222, 95% CI (1.117-1.336)], as well as mortality due to infectious diseases [HR = 1.606, CI (1.087-2.372)], cancer [HR = 1.129, CI (1.015-1.256)], respiratory diseases [HR = 1.381, CI (1.044-1.825)], and gastrointestinal diseases [HR = 1.658, CI (1.002-2.743)]. Subgroup analyses revealed a higher risk of all-cause mortality in prospective studies compared to retrospective studies, with significantly higher risks in studies from Europe and Asia.

Conclusions: AD is associated with an elevated risk of all-cause and cause-specific mortality, underscoring the need for improved monitoring and targeted interventions. Future research should incorporate more diverse populations and study designs.

Prospero identifier: CRD420251038553.

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: Systemic lupus erythematosus (SLE) is a prototypical autoimmune disorder characterized by production of autoantibodies targeting self-antigens. These autoantibodies form immune-complexes that deposit in various tissues, leading to complement activation, inflammation, and, ultimately, organ damage. The detection of specific autoantibodies is crucial for diagnosing SLE and for assessing disease activity.

Areas covered: A variety of autoantibodies are employed in clinical practice to assess the risk of different SLE manifestations and other systemic inflammatory diseases. These autoantibody specificities are integral to clinical decision-making procedures. Herein, we examine the most commonly evaluated autoantibodies and their associations with disease phenotypes. In addition, we discuss recent findings of novel autoantibodies in SLE and their clinical relevance and potential utility.

Expert opinion: In addition to the well-established autoantibody specificities routinely assessed in clinical practice for patients with a diagnosis of - or clinically suspected - SLE, recent studies have identified several new autoantibodies with potential clinical relevance. If these findings are validated through further research and accessible diagnostic assays are developed, these emerging autoantibodies could narrow the gap between first symptoms and classifiable disease and significantly enhance patient management by providing critical insights into the risk of specific SLE manifestations, thereby facilitating more timely and personalized interventions.

Introduction: Inflammatory myopathies (IM) are a heterogeneous group of systemic disorders characterized by chronic muscle inflammation. Cardiac involvement has historically been underrecognized, partially because of its subclinical presentation, and is associated with a poor prognosis, underscoring the urgent need for effective diagnostic strategies and therapeutic approaches. Cardiac magnetic resonance and its new mapping techniques appear as one of the most valuable instruments to detect myocardial involvement, thereby limiting the need for an endomyocardial biopsy when the underlying cause of cardiac dysfunction is unclear or when noninvasive imaging is inconclusive. Evidence-based data remains lacking regarding treatment strategies, and nowadays, immunosuppressive therapy constitutes the cornerstone of treatment.

Areas covered: In this review, we provide a summary of the current literature on myocarditis in the context of IM, with a focus on clinical manifestations, underlying pathophysiological mechanisms, diagnostic methods, and therapeutic strategies.

Expert opinion: We are currently in a privileged moment regarding IM, as there has never been a time with so many ongoing clinical trials. With growing awareness of cardiac involvement in IM, now is the time to focus research efforts on cardiac involvement in IM to address this underrecognized manifestation that carries significant morbidity and prognostic implications in patients with IM.

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: 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.