Expert Review of Clinical Immunology最新文献

Introduction: Primary cutaneous T cell lymphomas (CTCL) comprise a diverse group of malignancies with distinct and variable treatment options and prognoses. Differentiating between subtypes can be challenging due to overlapping heterogeneous clinical and histopathologic features, mandating careful clinicopathologic correlation for diagnosis. Mycosis fungoides (MF) is the most common subtype, whereas the less frequent Sézary syndrome (SS) is viewed at the more aggressive end of the MF/SS spectrum. Large cell transformation (LCT) is a rare phenomenon associated with poor prognosis, arising in a subset of patients with MF/SS, although the exact etiology and molecular pathogenesis remains unclear.

Areas covered: Progression of these diseases is influenced by a variety of immunologic factors. Our advancing understanding of immune pathways and tumor microenvironment may accelerate the development of targeted therapies. This review examines the immune-modulating effects of current and emerging therapeutic drugs for MF/SS. It encompasses both established clinical guidelines and emerging targeted agents currently under investigation in clinical trials.

Expert opinion: The treatment landscape for CTCL, especially advanced disease, is becoming increasingly focused on immunotherapies and biologic agents. These treatments have the potential to provide patients with more effective clinical outcomes. The development of synergistic combination therapy will also be important expanding therapeutic options in patients with advanced CTCL.

Introduction: Psoriatic arthritis (PsA) is an immune-inflammatory disease involving skin and synovial-entheseal compartments. The understanding of IL-17 biological function has revolutionized the understanding of PsA pathogenesis and, consequently, its therapeutic approach.

Areas covered: In this review article, we have outlined the primary evidence regarding the biological functions of IL-17A in PsA, and summarized data from randomized controlled trials (RCTs) on PsA and psoriasis approved secukinumab, ixekizumab, bimekizumab, brodalumab, and emerging IL-17 inhibitors.

Expert opinion: The biologic disease-modifying antirheumatic drugs (bDMARDs), secukinumab, and ixekizumab target interleukin-17A (IL-17A), and bimekizumab, which simultaneously neutralizes IL-17A and IL-17F, have demonstrated efficacy in treating both peripheral and axial articular manifestations of PsA, as well in improving skin involvement, enthesitis and dactylitis. Brodalumab, which inhibits the IL-17 receptor A (IL-17RA), represent an efficacious strategy for psoriasis.Continued research into the role of IL-17s in PsA pathogenesis is crucial for improving our understanding of the disease and developing more effective therapeutic strategies. Further research and advancements in biologic therapies will refine IL-17 inhibitory strategies, potentially improving outcomes for PsA patients, and other immune-mediated diseases.

Introduction: Urticaria is an inflammatory skin condition characterized by pruritic wheals, angioedema, or both. The global lifetime prevalence of chronic urticaria (CU) is estimated at 1.4%, with a slightly higher prevalence in children than adults. Although CU is not life-threatening, it significantly affects children's quality of life, affecting sleep, daily activities, and emotional well-being.

Areas covered: While many cases remit over time, a subset of children experiences refractory CU, which does not respond to standard or high-dose antihistamines. Treatment follows a stepwise approach, with second-generation H1-antihistamines, including dose escalation, as the first-line therapy. Omalizumab, a monoclonal anti-IgE antibody, is recommended for antihistamine-refractory cases. Other options include cyclosporine A and short-term corticosteroids for severe exacerbations. Emerging therapies, including dupilumab, Bruton's tyrosine kinase inhibitors, and barzolvolimab, show promise for refractory cases but require further research in pediatric populations.

Expert opinion: A stepwise treatment approach for pediatric refractory CU is presented in this review. Given its chronic nature and treatment challenges, ongoing research is crucial to optimize management strategies and improve patient outcomes.

Introduction: The involvement of the pulmonary parenchyma in rheumatoid arthritis (RA), characterized by the presence of interstitial lung disease (RA-ILD), represents one of the most common and potentially severe extra-articular manifestations of the disease. High-resolution computed tomography (HRCT) of the chest is considered the gold standard diagnostic technique; however, its reliance on ionizing radiation and the limited availability of imaging equipment make it challenging to perform repeatedly. Over the past decade, lung ultrasound (LUS) has emerged as a noninvasive and easily repeatable technique for detecting the presence of RA-ILD.

Areas covered: This narrative review summarizes the currently available evidence on the use of LUS in RA-ILD. It begins by defining the elementary lesions indicative of pulmonary involvement (B-lines and pleural irregularities) and provides an overview of LUS application in other connective tissue disease-associated interstitial lung diseases (CTD-ILDs).

Expert opinion: Current evidence suggests a promising role for LUS in the screening of RA-ILD, primarily based on the quantification of B-lines. Initially, a threshold of 10 B-lines was proposed, which has recently been lowered to 5, demonstrating good sensitivity and specificity in detecting RA-ILD. Future directions should focus on the role of pleural irregularities and the further standardization of the technique.

Introduction: Autoimmune bullous diseases (AIBDs) are a group of disorders caused by autoantibody-mediated damage to the skin and mucous membranes. Although AIBDs share immune-mediated mechanisms of epithelial disruption or basement membrane integrity, the precise cellular dynamics and molecular driver remain incompletely understood, hindering the development of targeted therapies.

Areas covered: In this review, we synthesize the cutting-edge findings from scRNA-seq studies (1978-2024) investigating AIBDs heterogeneity, focusing on pemphigus and bullous pemphigoid. Our analysis highlights how scRNA-seq has revealed disease-specific cell subpopulations, dysregulated cytokine/chemokine networks, and pathogenic intercellular crosstalk mechanisms.

Expert opinion: While scRNA-seq has significantly advanced our understanding of AIBDs pathophysiology by resolving cellular heterogeneity and dysregulated immune crosstalk, technical limitations persist. Challenges include the scarcity of high-quality clinical specimens, insufficient spatial resolution for microenvironmental mapping, and unvalidated functional significance of transcriptomic signatures. To address these limitations and advance the field, future research should focus on the integration of multi-omics approaches, spatial transcriptomics, and AI-driven analysis, which will enable comprehensive mapping of dynamic disease trajectories and identification of novel therapeutic targets. Translationally, validating scRNA-seq-predicted biomarkers in longitudinal cohorts will be critical for advancing precision medicine in these complex disorders.

Background: Severe asthma is a complex disease with persistent symptoms despite high-dose inhaled therapy. Tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), has shown efficacy across asthma phenotypes. However, identifying early responders remains a challenge. Basophils, key players in type 2 inflammation, may serve as predictive biomarkers.

Objective: We evaluated the presence of super-responder status after six months of Tezepelumab therapy and explored the predictive role of blood basophil levels.

Methods: A real-life, prospective study was conducted on 16 severe asthma patients. Super-responders were defined per Upham et al.'s criteria, adapted for a six-month assessment. Clinical, functional, and inflammatory parameters, including blood basophil counts, were analyzed.

Results: After six months, 62.5% of patients achieved super-responder status, with complete exacerbation elimination, reduced oral corticosteroid use, and improved asthma control. A significant logarithmic association (p = 0.019) was found between baseline basophil levels and super-responder status, indicating that higher basophil counts were associated with an increased likelihood of super-response. This finding was supported by a trend toward significance in ROC curve analysis (AUC = 0.800, p = 0.050), suggesting potential predictive value.

Conclusion: Tezepelumab demonstrates early efficacy in severe asthma, and baseline blood basophil levels may represent a promising biomarker for response prediction.

Introduction: The innate immune system's complement system and cGAS-STING pathway play crucial roles in pathogen defense and immune response modulation. Complement's role in cancer is multifaceted, affecting myeloid cells and T cell activities, while intracellular complement (complosome) participates in cellular processes like metabolism and autophagy. STING's activation influences tumor dynamics through NF-κB pathway interactions, enhancing or suppressing tumor responses. The interplay between complement and cGAS-STING pathways suggests potential regulatory crosstalk affecting immune responses, warranting further investigation.

Areas covered: We review the functions of the complement system and the cGAS-STING pathway in pathogen clearance and tumor development. The focus is on exploring the intricate interplay between these pathways and discussing its implications for disease pathogenesis ;(PubMed: 1983-2024).

Expert opinion: Such insights into these pathways could guide therapeutic strategies targeting immune modulation in oncology and autoimmune disorders, emphasizing the need to understand their complex roles in health and disease.

Introduction: About 75% of psoriasis cases in the female population affect women under 40 years of age, hence possibly involving pregnancy or lactation periods. Data concerning common topical and systemic treatments for psoriasis during pregnancy and lactation are limited given the fact that pregnancy is an exclusion criterion for clinical trials.

Areas covered: The aim of our review is to provide an overview of currently available treatments in women with childbearing potential, pregnancy, and breastfeeding, both topical and systemic, including biological therapies and small molecules.

Expert opinion: The choice of the most appropriate treatment must be made on a case-by-case basis, assessing the risk-benefit ratio for the mother and the fetus or offspring. We recommend multidisciplinary management of the patient and consultation of data, if available, from national safety registers on pregnancy outcomes in exposed mothers.

Introduction: Diabetic kidney disease (DKD) is one of the most common causes of chronic kidney disease, leading to end-stage kidney disease (ESKD), and is one of the most significant complications associated with diabetes mellitus. Furthermore, the medical costs of dialysis therapy associated with ESKD are high, and financial strain is a major problem. This review first focuses on the mechanisms of DKD progression and exacerbation, and then describes the 'DKD fantastic four,' which we advocate as the latest DKD treatment.

Areas covered: In DKD, increase in the extracellular matrix of mesangial cells is attributed to transforming growth factor-β/Smad1/type 4 collagen signaling, whose effects are enhanced by angiotensin II signaling.DKD activates protein kinase C (PKC)d, leading to dephosphorylation of vascular endothelial growth factor receptor-2 and reduction of its downstream effects, thereby inducing podocyte apoptosis. PKCβ inhibits insulin receptor substrate 1/Akt/endothelial NO synthase signaling in glomerular endothelial cells.

Expert opinion: Recently, sodium-glucose co-transporter 2 inhibitors have been shown to reduce the risk of progression of nephropathy. Additionally, glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptides elicit vasoactive effects, reducing the risk of DKD. Finerenone, a non-steroidal mineralocorticoid receptor antagonist, reduces the composite renal endpoint without causing severe hyperkalemia.

Introduction: Chronic airway inflammatory diseases mainly comprise chronic rhinosinusitis (CRS), allergic rhinitis (AR), asthma, cystic fibrosis (CF), and chronic obstructive pulmonary disease (COPD). Epithelial cells fulfill a protective role as a barrier; however, when stimulated, these cells also release a variety of cytokines that attract and activate immune cells, including macrophages, neutrophils, and T-lymphocytes. Excessive activation and aggregation of immune cells disrupts the balance of the cellular microenvironment, and leads to impaired immune defense of the airway mucosa, which can further exacerbate an inflammatory response.

Areas covered: In this article, we discuss the key cytokines and immune pathways involved in epithelial-immune cell interactions, and we detail discoveries in the emerging field of single-cell sequencing and summarize monoclonal antibody-targeted therapies. A comprehensive search was conducted using the search terms 'epithelial cell,' 'immune,' 'interaction,' 'cytokines,' 'asthma,' 'chronic sinusitis,' 'allergic rhinitis,' 'monoclonal antibodies,' and 'single-cell sequencing' by querying Google Scholar and PubMed.

Expert opinion: The intricate pathophysiology of airway inflammation remains to be fully elucidated. Emerging technologies, such as single-cell sequencing, have led to a more comprehensive characterization of the immune mechanisms underlying the pathophysiology of airway inflammatory diseases, which points the way to further precision medicine in the future.