Expert Review of Clinical Immunology最新文献

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: 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.

Introduction: The tumor microenvironment is a dynamic and balanced internal environment that accompanies the whole process of tumor development, invasion, and metastasis. Immune checkpoint therapy, chimeric antigen receptor cell therapy, oncolytic virus therapy, and bispecific antibody therapy are the most anticipated immunotherapy methods. These therapies break the microenvironment conducive to tumor growth by regulating anti-tumor immunity. The underlying characteristics of the tumor immune microenvironment are the key scientific issues to break the bottleneck of solid tumor immunotherapy. With the rapid development and application of single-cell sequencing technology and spatial oncology technology, scientists have gradually recognized more complex details of cell-cell interaction in the tumor microenvironment.

Areas covered: We review the latest research progress in tumor immune escape, tumor metabolic reprogramming, and neuroimmunity [PubMed database published between 2000 and 21 May 2025]. We analyze the effects of these biological processes on anti-tumor immunity, to seek breakthroughs for the design of combined immune therapy. We also summarize the latest research on major immunotherapies mentioned above.

Expert opinion: Through the integration of frontier and hot basic scientific issues and the design of clinical trials, we hope to identify the potential combination treatment plan for immunotherapy to overcome the tumor microenvironment of solid tumors.

Introduction: Alopecia areata (AA) is an immune-mediated non-scarring alopecia characterized by T lymphocytes attacking hair follicles (HFs), which has a seriously harmful impact on physical and mental health. The challenges in the treatment of AA lie in the recurrence after drug withdrawal and the treatment-resistant cases. Sequential immunotherapy may be able to address some of these issues.

Areas covered: As a new treatment model, sequential immunotherapy employs temporally coordinated immunomodulatory interventions with distinct therapeutic focuses. For patients with recurrence, the purpose of sequential immunotherapy is to restore the immune privilege and immune homeostasis of HFs. For cases that are difficult to treat, alternative strategies are needed to promote hair regrowth. Based on systematically selected articles from the PubMed database, this review, in conjunction with the immune pathogenesis of AA, carefully evaluated the sequential immunotherapy strategies.

Expert opinion: The efficacy and safety of AA treatment remain pressing challenges in current clinical practice. The sequential immunotherapy strategy, which combines initial intensive immunosuppression with subsequent maintenance therapy, demonstrates significant potential for addressing the dynamic nature of disease progression. This is achieved through stage-specific modulation of inflammatory cascades and restoration of immune tolerance.

Introduction: Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide. In this work, we reviewed the clinical management of FMF in adults also considering the possible development of additional issues in the long-term.

Areas covered: A typical feature of FMF is the childhood onset, however, adult patients have been increasingly documented. The suspicion of adult onset FMF should be formulated when assessing a clinical picture characterized by systemic inflammatory episodes, apparently unprovoked, excluding other causes according to the diagnostic procedures for fever of unknown origin. The suspected clinical picture for autoinflammatory disease should not fulfill the criteria for diverse inflammatory diseases. Usually, the patients do not benefit following the administration of conventional immunosuppressants. Adult patients with FMF may experience some specific issues of the long-term disease, such as liver involvement and kidney failure, to be regularly monitored. Fertility concerns may also emerge with adulthood in patients with FMF, which should be carefully managed.

Expert opinion: The possibility of occurrence of FMF is not completely excluded in adult patients, despite it could be characterized by atypical or delayed-onset presentations. Thus, raising the awareness toward the disease is of critical importance in improving the outcome of these patients.

Introduction: Immunotherapies such as CAR T-cell therapy and immune checkpoint inhibitors (ICIs) have transformed pediatric cancer treatment but are increasingly associated with severe central nervous system (CNS) immune-related adverse events (irAEs), which remain poorly understood in children.

Areas covered: This review summarizes current knowledge on CNS irAEs in children receiving CAR T-cells, ICIs, and monoclonal antibodies. Based on a narrative literature review from PubMed, Scopus, and Web of Science (2010-2025), it focuses on pediatric neurotoxicity, immunopathogenesis, and age-specific vulnerabilities, including an immature blood-brain barrier, reduced naive T-cells, and chronic inflammation. Common irAEs include ICANS, autoimmune encephalitis, Guillain-Barré syndrome, and hypophysitis.

Expert opinion: Managing CNS immune toxicity in pediatric immunotherapy is a critical challenge that requires early detection, ongoing monitoring, and age-appropriate interventions. Progress depends on identifying predictive biomarkers and tailoring immunomodulatory strategies to enhance safety while preserving efficacy.

Introduction: Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a rare and chronic fibroinflammatory condition hallmarked by tumefactive lesions that can affect nearly any organ of the body and lead to fibrotic organ destruction. Parenchymal and non-parenchymal affection of the kidney and urogenital tract are subsumed under the umbrella term IgG4-related kidney disease (IgG4-RKD), which is a severe and quite common organ manifestation in IgG4-RD. The immunopathogenesis in IgG4-RD is depicted by a complex interplay of distinct B- and T-cell subsets, excessive antibody production, a unique cytokine environment and the development of exuberant fibrosis. Scientific advancements over the last two decades have fostered to explore a broad repertoire of pharmacological interventions starting from B-cell depleting agents and extending to modulators of T-cell co-stimulation.

Areas covered: The aim of this review is to a) provide an overview of the current knowledge on IgG4-RKD with an emphasis on the unique properties of renal histopathology and immunopathogenesis and b) overview novel pharmacological interventions targeting B cells, T cells, and beyond.

Expert opinion: Speculating on a potential scenario that dominates IgG4-RD's treatment reality in 5 years, the advent of integrative treatment strategies combining both B- and T-cell targeting agents is conceivable.

Introduction: The treatment of rheumatic diseases has dramatically changed thanks to the availability of novel drugs. Besides clinimetric indexes, there is a strong need for valid, rapid, and sensitive-to-change, possibly noninvasive, and low-cost instruments to accurately assess treatment outcomes and to select the target patient.Musculoskeletal ultrasound (MSUS) has recently been shown to be able to respond to such needs. Indeed, it seems instrumental as a disease outcome measurement as it is capable to capture both the inflammatory state and the structural damage, allowing clinicians to accurately assess a patient's condition and make informed treatment choices.

Areas covered: In this narrative review, the authors summarize the up-to-date knowledge on how MSUS can guide treatment for patients, with rheumatic diseases focusing on rheumatoid arthritis (RA) and psoriatic arthritis (PsA), particularly helping clinicians in monitoring disease activity and in identifying responses to currently approved biological and targeted synthetic disease modifying anti-rheumatic drugs (bDMARDs and tsDMARDs).

Expert opinion: So far, knowledge of the evolving pattern of MSUS is paramount to avoid misinterpretations. However, usage of US standardized clinimetric indexes as well as the choice of the target joints are still missing points in the daily clinical workflow and the decision-making process.

Background: Sjögren's Disease (SjD) primarily affects exocrine glands, but some patients develop axial manifestations. This study investigated the prevalence and predictors of sacroiliitis in primary SjD and proposed a clinical risk score.

Methods: In this multicenter cross-sectional study, 144 patients fulfilling 2016 ACR/EULAR criteria for SjD underwent clinical, laboratory, and imaging evaluation. Sacroiliitis was defined by radiographic and/or MRI criteria. Logistic regression identified predictors, and ROC analysis assessed diagnostic performance.

Results: Sacroiliitis was present in 16.7% of patients. Independent predictors were inflammatory back pain (OR 18.7, p < 0.001) and smoking (OR 9.8, p = 0.003). HLA-B27 showed borderline significance (p = 0.051). Anti-SSB was only borderline (p = 0.098) and was not retained in multivariate analysis. ROC analysis showed good performance for smoking (AUC 0.81), inflammatory back pain (AUC 0.79), and HLA-B27 (AUC 0.72). A composite Axial Involvement Risk Score (0-3) integrating these predictors achieved excellent accuracy (AUC 0.91); a cutoff ≥1 yielded 100% sensitivity and 63% specificity.

Conclusion: Axial involvement in SjD may represent a distinct phenotype. The score may support early recognition of sacroiliitis and guide clinical decision-making.