Expert Review of Clinical Immunology最新文献

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.

Introduction: Inborn errors of immunity with atopic phenotypes (IEIwA) represent a growing and complex subset of monogenic disorders that manifest primarily through severe and multifaceted allergic symptoms. These conditions bridge the fields of immunodeficiency and atopy, posing significant diagnostic and therapeutic challenges.

Areas covered: A literature search was performed via the online database PubMed, including all publication years 2021-2024, with the objective of identifying the most recent advancements in the field of IEIwA. This review provides an updated synthesis of the immunogenetic mechanisms underlying IEIwA, categorizing them by pathophysiological pathways, including impaired T cell receptor signaling, cytokine dysregulation, T cell repertoire restrictions, regulatory T cell dysfunction, metabolic abnormalities, and skin barrier defects. Advances in genomic technologies, especially whole-exome/genome sequencing, have refined the classification and recognition of these disorders. Moreover, the review highlights red flags that may aid in differentiating monogenic IEIwA from multifactorial allergic conditions. Emerging targeted therapies, such as monoclonal antibodies and small molecules, offer new avenues for precision medicine, though curative treatments like hematopoietic stem cell transplantation remain essential for many conditions.

Expert opinion: This review underscores the need for heightened awareness, early recognition, and tailored management strategies to improve outcomes in patients with IEIwA.

Introduction: Interleukin-17 (IL-17), a proinflammatory cytokine primarily produced by Th17 cells, plays a complex role in transplant immunology. Its involvement in graft-versus-host disease (GvHD) and immune regulation following hematopoietic cell transplantation (HCT) has garnered significant clinical interest, though findings remain inconsistent.

Areas covered: This narrative review summarizes clinical studies in human HCT recipients investigating IL-17 cytokine levels, Th17 cell activity, and IL-17 gene polymorphisms associated with transplant outcomes. While several studies report associations between elevated IL-17 or Th17 levels and increased GvHD risk, results vary widely due to differences in study design, patient populations, and measurement methods.

Expert opinion: IL-17 is a promising, though context-dependent, biomarker and therapeutic target in HCT. Its dual roles in promoting inflammation and supporting antimicrobial defense complicate therapeutic modulation. Future studies should focus on standardized assays, multi-omics approaches, and longitudinal designs to clarify its clinical utility. Tailored strategies that modulate IL-17 without impairing immune reconstitution or graft-versus-leukemia effects are likely to guide future interventions.

Introduction: T regulatory cells (Tregs) are key modulators of the immune system with dual roles. While protective against autoimmunity, Tregs can exhibit immunosuppressive capabilities, allowing the tumor to evade immune recognition and destruction, and favoring tumor progression. Targeting Tregs to reduce their immunosuppressive ability offers a promising strategy to boost anti-tumor immunity and improve cancer treatment outcomes.

Areas covered: This review explores the role of Tregs in the immune system, delves into their contribution to cancer and tumor progression, and highlights therapeutic strategies targeting Tregs, along with innovative delivery systems.

Expert opinion: Targeting tumor-infiltrating regulatory T cells (Tregs) represents a promising but complex approach in cancer immunotherapy. However, its success is limited by the risk of autoimmunity, inefficient intratumoral delivery, and patient immune heterogeneity. Precision strategies integrating biomarker-guided stratification, single-cell, and spatial profiling can improve selectivity and therapeutic outcomes. Identifying tumor-specific Treg markers and distinguishing stable, suppressive Tregs from more plastic or 'fragile' subsets are essential for advancing targeted immunotherapies. Partial functional reprogramming of tumor-resident Tregs, rather than their complete depletion, offers a strategy to weaken their suppressive capacity while retaining peripheral immune regulation, thus promoting local anti-tumor responses without disrupting tolerance.

Background: In response to the clinical dilemma of insufficient immune treatment response rate for lung adenocarcinoma (LUAD), this study aims to analyze the regulatory mechanism of the TCF3/VEGFA axis on CD8⁺ T cells' function.

Research design and methods: Bioinformatics analysis predicted the upstream transcription factors of VEGFA. Dual luciferase and ChIP assays verified the binding relationship between VEGFA and TCF3. WB detected the expression of VEGFA, NF-κB-related markers and PD-L1. Flow cytometry and immunofluorescence detected the expression of PD-L1. The cytotoxicity efficiency of CD8⁺ T cells was evaluated in a co-cultivation system. A subcutaneous LUAD mouse model was constructed to verify the role of TCF3/VEGFA in vivo.

Results: VEGFA was transcriptionally activated by its upstream transcription factor TCF3 (p < 0.05). Overexpressing TCF3 weakened the inhibitory effect of VEGFA knockdown on NF-κB-related markers and PD-L1 expression and the promotion of CD8⁺ T cell cytotoxicity (p < 0.05). in vivo experiments also confirmed that overexpressing TCF3 reversed the anti-tumor effect of VEGFA knockdown (p < 0.05).

Conclusions: This article reveals that the TCF3/VEGFA axis enhances the expression of PD-L1 in LUAD by activating the NF-κB signaling pathway, thereby weakening the cytotoxicity of CD8⁺ T cells.