Expert Review of Clinical Immunology最新文献

Introduction: Alopecia areata (AA) is an autoimmune non-scarring hair loss that involves collapse of hair follicle immune privilege. Genetic susceptibility, environmental stressors, and aberrant interaction between dendritic cells, CD4⁺ and CD8⁺ lymphocytes, drives follicular destruction and disrupts hair cycling. Pro-inflammatory cytokines, including IL-15 and IFNγ, and downstream JAK-STAT pathway activation, are central to disease progression.

Areas covered: Though variably effective, conventional treatments including corticosteroids, contact sensitizers, phototherapy, and systemic immunosuppressants remain standard therapeutic approaches for AA in many clinics. However, insights into Th1, Th2, and Th17 cell activity, along with the cytokine signals involved (IFNγ, IL-15, IL-4/13, IL-17/23), and an emerging understanding of immune checkpoints in AA (PD-1/PD-L1, CD28/CD80/CD86/CTLA4, OX40/OX40L), are shaping the clinical investigation of new AA treatments; particularly JAK inhibitors and biologics targeting specific signaling pathways.

Expert opinion: Heterogeneity in AA clinical presentation, molecular pathogenesis, and variable treatment responses suggests a biomarker-driven patient stratification system is needed to optimize drug selection, reduce trial-and-error therapy, and minimize side-effect risk. In the longer term, approaches that couple rapid immunosuppression with strategies to regenerate follicular immune privilege and tolerize autoreactive memory T cells are likely to shift AA therapeutic approaches away from chronic immune suppression toward true disease-modifying or curative interventions.

Background: This study evaluated clinician adherence to unrestricted antinuclear antibody (ANA) and subserology test requests, comparing rheumatologists and other specialists, and assessed the financial impact of inappropriate orders.

Research design and methods: We analyzed 43,691 patients tested for ANA IIF from January 2022 to June 2024. ENA profile immunoblot requests without appropriate ANA IIF positivity were categorized by specialty.

Results: Rheumatologists ordered 11,581 ANA IIF tests (26.51%), while non-rheumatology physicians ordered 32,110 (73.49%). Of ANA IIF-negative results, 55.82% had ENA immunoblots, with rheumatologists (73.97%) and non-rheumatologists (50.42%) contributing to unnecessary requests. After implementing reflex testing, specialist training, and ELISA, the ENA immunoblot claim rate decreased from 58.44% to 20% within one year, resulting in an annual savings of €121,000.

Conclusions: Reflex testing and laboratory-guided algorithms reduce unnecessary orders, maintain diagnostic accuracy, and achieve significant cost savings through enhanced collaboration between clinicians and laboratories.

Introduction: Langerhans Cell Histiocytosis (LCH) is a rare neoplastic disorder characterized by monoclonal proliferation and tissue infiltration by pathological dendritic cells, often associated with abnormal activation of the MAPK signaling pathway and BRAF V600E mutation. The diagnosis is established through clinical, radiological, and histopathological evaluation. It can manifest in various organs, notably bones, skin, and the hypothalamic-pituitary axis. The assessment of central nervous system (CNS) involvement in LCH includes both parenchymal and non-parenchymal structures, including craniofacial bones, hypothalamic-pituitary axis, and meninges.

Areas covered: We used the PubMed database and reviewed relevant English-language literature published from 1989 to 2024. The sources included original researches, reviews and case reports, excluding editorials and letters to the editor. This review focuses on the existing evidence regarding the imaging, clinical, and pathological aspects of CNS, cranial and spinal bones involvement in LCH and its differential diagnosis.

Expert opinion: Imaging plays an essential role in properly diagnosing, guiding biopsy and monitoring treatment. Computed tomography (CT) is particularly helpful for evaluating bone involvement, while magnetic resonance imaging (MRI) is preferred for assessing parenchymal brain and meningeal lesions. The disease can present in either tumoral or neurodegenerative forms, manifesting with varied symptoms depending on the affected region.

Introduction: The rising global prevalence of eosinophilic esophagitis (EoE) has made it a major topic of interest in both Clinical Immunology and Gastroenterology. Despite advances in understanding its physiopathology, optimal long-term management remains challenging due to disease heterogeneity and variable treatment responses. An integrated, patient-centered approach can be valuable in clinical practice, improving outcomes by tailoring treatment strategies to individual patient needs.

Areas covered: This review explores the current therapeutic options of EoE, including proton pump inhibitors (PPIs), topical corticosteroids, elimination diets, and biologic agents, focusing on treatment efficacy, limitations, and patient-centered factors such as quality of life, treatment adherence, and comorbid atopic conditions. The article also examines recent guidelines and the rationale behind personalized therapy approaches. A comprehensive review of the current literature on personalized therapy for EoE has been conducted, highlighting recent developments in treatment strategies and individualized patient care approaches.

Expert opinion: There is no one-size-fits-all therapeutic strategy for EoE. Given the complexity of patient profiles, including immunologic phenotypes, psychological attitudes, and socioeconomic factors, therapeutic choices must be personalized. Shared decision-making is essential to align treatment plans with patient values and improve both clinical outcomes and long-term adherence.

Introduction: Hepatocellular carcinoma (HCC) is a major cause of cancer-related death globally, characterized by an immunosuppressive tumor microenvironment (TME) that impairs immune surveillance. Immunotherapy has emerged as a transformative option; however, durable responses remain limited. The purpose of this review is to synthesize recent advances in HCC immunology, immunotherapy, and the TME.

Areas covered: Literature was identified via PubMed and ClinicalTrials.gov (January 2001-May 2025), focusing on clinical and translational studies. We outline the immunological landscape of HCC, emphasizing the roles of T cells, natural killer cells, macrophages, dendritic cells, myeloid-derived suppressor cells, and regulatory T cells in shaping tumor immunity. TME components include cancer-associated fibroblasts, tumor-associated macrophages, suppressive cytokines, angiogenesis, hypoxia, metabolic reprogramming, and the gut-liver axis. Interactions with immunotherapy, mechanisms of resistance, and combination strategies were described. Emerging biomarkers - such as tertiary lymphoid structures, PD-L1, tumor mutational burden, gene signatures, and gut microbiota - are reviewed relative to patient stratification.

Expert opinion: Immunotherapy has reshaped HCC management, but resistance, biomarker limitations, and heterogeneity remain major challenges. Advances will require TME reprogramming, multi-parametric biomarkers, and personalized strategies. Integration with targeted and locoregional approaches may achieve durable responses and move toward precision immuno-oncology, transforming HCC into a manageable or curable disease.

Introduction: Human T-lymphotropic virus type-1 (HTLV-1) is a retrovirus associated with the development of various diseases. HTLV-1 contributes to the development of several disorders that mimic autoinflammation. The pathogenic processes that underlie the emergence of such auto-inflammation-like conditions following HTLV-1 infection remain a subject of ongoing scientific debate and investigation.

Areas covered: This study provides a comprehensive review of the pathophysiology of HTLV-1-associated inflammatory diseases with an emphasis on the role of regulatory T cells and the plasticity of these cells in the development of such diseases through a selection of the most relevant and recent papers in PubMed and the Web of Science database.

Expert opinion: Recent evidence suggests that HTLV-1 infection induces the expansion of regulatory T cells (Tregs) with high plasticity, which can convert into effector T cells that promote immune deviation toward autoinflammation, including T-helper1 (Th1) cells, T-helper17 (Th17) cells and a novel effector T helper cell subpopulation with particular specificity for HAM/TSP called T_HAMs. The development of novel therapeutic strategies targeting these cells paves the way for new therapeutic strategies, which hold significant promise for providing more favorable treatment outcomes for involved individuals and ameliorating patients' symptoms.

Background: Cockroach allergens remain underrecognized in allergic diseases, despite growing evidence of their clinical impact. This study investigated cockroach sensitization prevalence in allergic rhinitis (AR) patients and its cross-reactivity with house dust mite (HDM) and seafood allergens.

Methods: 110 AR patients sensitized to at least one of eight allergens: Periplaneta americana (PA), Blattella germanica (BG), Dermatophagoides pteronyssinus (DP), Dermatophagoides farinae (DF), Blomia tropicalis (BT), shrimp, crab and squid were enrolled. Sensitization was assessed using skin prick testing (SPT) and sIgE assays and cross-reactivity by direct and inhibition enzyme-linked immunosorbent assays (ELISA).

Results: HDM allergens were the most sensitized (BT: 90%, DP: 50.9%, DF: 49.1%), followed by cockroach allergens (PA/BG: 39.1%) and seafood allergens (shrimp: 30.9%, crab: 25.5%, squid: 24.5%). sIgE testing yielded comparable results. BT demonstrated the highest prevalence. Cross-reactivity was pronounced between cockroach and HDM allergens, followed by intra-cockroach species. DP had the highest frequency of cross-reactivity among HDM allergens, while BG had a higher cross-reactivity with HDM (44.5%) than PA (40.9%). Cockroach allergens exhibited minimal cross-reactivity with seafood allergens.

Conclusions: SPT and direct ELISA performed equally, demonstrating their usefulness for assessing sensitization. Cockroach allergens interact strongly with HDM but have limited cross-reactivity with seafood.

Introduction: Eradicating measurable residual disease (MRD) may represent the final hurdle in curing ALL. The introduction of immunotherapies alone or in combination with other agents to therapies, including induction therapy, consolidation therapy, maintenance therapy, preemptive therapy and salvage therapy, was superior to chemotherapy alone in eradicating MRD during the course of treatment, leading to improved survival.

Areas covered: We provide a concise overview of the techniques used for MRD detection. We focus on the application of immunotherapies for MRD eradication at different treatment timepoints, and the factors associated with poor outcomes in patients receiving immunotherapies. We also discuss the underlying mechanisms of immunotherapy resistance in leukemia. Additionally, we highlight the importance of characterizing residual disease and designing prospective clinical trials, as these efforts may contribute to the development of novel immunotherapies and help determine which currently available immunotherapies are most effective.

Expert opinion: Immunotherapies represent a breakthrough and are currently changing the status quo of ALL therapy. Future research should focus on biomarker-directed individual immunotherapy, mechanism-driven development of new therapies, and clinical trials to identify the best immunotherapy.