Expert Review of Clinical Immunology最新文献

Introduction: For decades, the first-line treatment for kidney protection in people with type 1 diabetes (T1D) and chronic kidney disease (CKD) has been limited to intensive glycemic control, renin-angiotensin system blockers and managing modifiable risk factors. Accordingly, risk of CKD progression has remained unacceptably high, emphasizing the need for novel kidney protective therapies in T1D.

Areas covered: This review summarizes the recent evidence supporting the use of existing treatments used for kidney protection in people with type 2 diabetes (T2D) for potential repurposing for people with T1D. First, we highlight the putative structural and functional changes that actively contribute to CKD progression and highlight key hemodynamic, pro-inflammatory, and kidney injury risk markers in T1D. Next, we discuss emerging nephroprotective therapies targeting these pathophysiological factors, review mechanistic studies that have assessed kidney benefits of these agents in T1D, and highlight ongoing kidney-focused trials in T1D, including SUGARNSALT (NCT06217302), FINE-ONE (NCT05901831) and REMODEL-T1D (NCT05822609).

Expert opinion: Several medications have become available that could potentially transform CKD care in T1D. It is essential to devise strategies that could address the treatment landscape for kidney protection in T1D by assessing the risk-benefit calculus and expanding the nephrologist's toolkit for minimizing kidney risk in T1D.

Objectives: IL17A, part of the IL17 cytokine family, is a pivotal player in synovitis present in RA patients. This research focused on assessing how the IL17A rs2275913 genetic variation influences IL17A serum concentration, disease progression, and prognosis in Egyptian RA patients.

Methods: It encompassed a group of 100 healthy individuals and 100 RA patients. The rs2275913 genetic polymorphism was analyzed in both groups using the Taqman genotyping assay. Additionally, IL17A serum concentration was examined through the ELISA technique.

Results: RA patients demonstrated significantly elevated IL17A serum levels compared to control subjects (122 ± 32.5 Pg/mL vs 20.5 ± 2.8 Pg/mL, p < 0.001). Moreover, the prevalence of the rs2275913 G allele was higher in RA patients than in normal individuals (p < 0.001). Those with the GG genotype exhibited increased levels of all parameters related to disease severity and activity. Individuals with the GG genotype exhibited elevated IL17A serum levels in comparison to those with GA and AA genotypes (127.9 ± 29.9 Pg/mL vs 111.1 ± 34.6 Pg/mL, p = 0.013).

Conclusion: In summary, the IL17A rs2275913 gene polymorphism has an impact on IL17A serum production, therefore it has role in diseases pathogenesis, and it is linked to increased disease severity in Egyptian RA patients.

Introduction: Choosing the right biologic for the right patient is challenging. It requires evaluating patient characteristics and disease manifestations, understanding the scientific evidence supporting each biologic's efficacy and safety, and using a shared decision-making strategy with the patient.

Areas covered: Based on a comprehensive review of the literature, in this narrative review we explore the latest approaches on the optimal selection of biologics in severe asthma.

Expert opinion: Biologics target different inflammatory pathways. The choice of biologic depends on biomarker profiles, clinical phenotype and endotype of the disease and its associated comorbidities. A structured approach using biomarkers is essential to guide personalized treatment decisions. Exacerbation history, corticosteroid dependence, and comorbidities all influence therapeutic selection. Asthma is challenging to treat because it is heterogeneous, symptoms change over time and biomarkers lack precision. Researchers are recognizing the need for combination biologic therapy and improved biomarker-driven strategies. However, biologic selection is complex due to overlapping inflammatory pathways and variable treatment response. Emerging strategies, including multi-biomarker panels, multi-omics approaches, and machine learning-driven decision making, aim to refine asthma phenotyping/endotyping and thus optimize treatment outcomes. Real-world studies, pragmatic clinical trials, and head-to-head comparisons of biologics are key to advancing precision medicine and improving long-term asthma management.

Introduction: This network meta-analysis (NMA) of randomized controlled trials (RCTs) aimed to evaluate the efficacy and safety of pharmacotherapies for progressive fibrotic-interstitial lung diseases (PF-ILDs) to identify optimal treatments.

Methods: We searched for RCTs on PF-ILD [idiopathic pulmonary fibrosis (IPF), connective tissue disease-ILD (CTD-ILD), chronic hypersensitivity pneumonitis (CHP), and pulmonary sarcoidosis] pharmacotherapies until 5 June 2025. NMA assessed efficacy [forced vital capacity, diffusing capacity of lungs for carbon monoxide, 6-minute-walk distance] and safety [serious adverse events (SAEs) and all-cause mortality] (PROSPERO: CRD42024554475).

Results: We included 65 studies (13,521 participants) for 48 drugs in IPF, 10 studies (1,508 participants) for eight drugs in CTD-ILD, four studies (259 participants) for three drugs in CHP, and nine studies (525 participants) for nine drugs in pulmonary sarcoidosis. In IPF, pirfenidone, nintedanib, and IFNγ-1b slowed lung function decline and reduced mortality. In CTD-ILD, pirfenidone, nintedanib, tocilizumab, and cyclophosphamide improved lung function and reduced mortality, with higher SAEs for nintedanib and cyclophosphamide. Pirfenidone and prednisolone benefited CHP, while budesonide improved lung function in pulmonary sarcoidosis.

Conclusions: Anti-fibrotic drugs - Pirfenidone and nintedanib effectively slow disease progression and reduce mortality in PF-ILDs. Emerging therapies like IFNγ-1b warrant further research, underscoring the need for large, high-quality RCTs.

Objectives: The main purpose of this study is to investigate the specific role of SPC25 in the anti-tumor immune process of Natural killer (NK) cells in lung adenocarcinoma (LUAD).

Methods: The differentially expressed gene SPC25 was screened by the Cancer Genome Atlas database. The effect of SPC25 on the anti-tumor immunity of NK cells was evaluated by immunofluorescence, flow cytometry, lactate dehydrogenase kit, and enzyme-linked immunosorbent assay. The influence of SPC25 on glutamine (GLN) metabolism was examined by the GLN metabolism-related kit and Western blot. The interaction between SPC25 and TFDP1 was assessed by luciferase reporter gene detection and ChIP.

Results: SPC25 was overexpressed in LUAD (p < 0.0001), being capable of reducing levels of cytotoxicity and cytokines in NK cells. SPC25 repressed the function of NK cells by activating GLN metabolism (p < 0.0001). Mechanistically, TFDP1 was a transcriptional activator of SPC25. Knocking down TFDP1 hindered GLN metabolism (p < 0.05) and potentiated NK cell killing ability against LUAD cells, while overexpression of SPC25 reversed the effects of TFDP1 knockdown.

Conclusion: This study intended to verify the inhibitory effect of TFDP1 on NK cell anti-tumor immunity by activating SPC25-mediated LUAD glutamine metabolism.

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.