Expert Review of Clinical Immunology最新文献

Background: To describe the clinical and epidemiological characteristics of Behçet's disease (BD) in a sample from northwestern Algeria and compare them with data from other ethnic groups.

Research design and methods: This is a retrospective study conducted between 2016 and 2024, including patients with BD followed at the internal medicine and dermatology departments of the Oran University Hospital Center. Demographic and clinical data were collected and analyzed.

Results: Among a total of 85 patients, oral ulcers were the most common symptom (98.82%), followed by genital ulcers (76.47%) and skin lesions (74.12%). Neurological and vascular involvement were less frequent, affecting 35.29% and 25.88% of patients, respectively. A male predominance was observed, with a sex ratio of 1.74. Analysis of clinical manifestations by gender revealed a higher frequency of ocular (p = 0.015, 95% CI: [0.23, 2.07]) and vascular (p = 0.012, 95% CI: [0.37, 3.00]) lesions in male patients. The mean age at diagnosis was 27.13 ± 6.27 years.

Conclusions: Oral and genital ulcers are the most common manifestations. Differences in the distribution of clinical signs according to gender were observed.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition prevalent among children worldwide. Systemic inflammation is a key factor in its pathophysiology. Correlating blood markers with Eczema Area and Severity Index (EASI) can reveal information about the severity and activity of the disorder, allowing for more focused treatment.

Methods: A retrospective analysis was conducted on 22 patients aged 3 months to 18  years. Blood parameters, such as Eosinophil Relative Count (ERC), Neutrophil/Lymphocyte Ratio (NLR), Eosinophil/Lymphocyte Ratio (ELR), and Basophil/Lymphocyte Ratio (BLR), were correlated with the Eczema Area and Severity Index (EASI).

Results: A strong positive correlation was observed between EASI scores and ERC (r = 0.69, p < 0.001) and with ELR (r = 0.71, p < 0.001). No statistical significance was seen between EASI scores and the NLR (r = 0.2059, p = 0.3578) and BLR (r = 0.1026, p = 0.6494). No significant association was found between age and EASI scores (r =  -0.0351, p = 0.8767).

Conclusions: ERC and ELR have the potential to serve as objective blood markers for assessing AD severity. However, more research in pediatric populations with a larger sample size is needed to establish a conclusive association for clinical practice.

Introduction: The Janus kinase/signal transducer and activator of transcription signaling pathway orchestrates crucial aspects of immune regulation, including cytokine signaling, cellular proliferation, differentiation, and apoptosis. Dysregulation of this pathway due to gain- or loss-of-function mutations significantly contributes to the development of inborn errors of immunity and various immune-mediated disorders. Understanding the molecular basis of these abnormalities is fundamental for enhancing diagnostic precision and developing targeted therapies.

Areas covered: A bibliographic search was conducted in PubMed and MEDLINE for articles published up to June 2025. The review offers a comprehensive overview of the structural and functional features of JAK/STAT family proteins, the intrinsic regulatory mechanisms, and the immunopathological consequences of STAT1, STAT3, and STAT6 gain-of-function diseases. Recent clinical advances, particularly the therapeutic impact of JAK inhibitors (JAKinibs) and emerging novel molecules, are critically discussed, emphasizing the integration of molecular insights into clinical practice.

Expert opinion: Advances in the molecular characterization of JAK/STAT pathway dysregulation have opened new avenues for precision medicine approaches. While JAKinibs have shown promising outcomes, further research is needed to optimize therapeutic strategies, identify predictive biomarkers, and refine patient selection to maximize clinical benefits. Novel targeted therapies can reshape the management of JAK/STAT-related diseases in the coming years.

Introduction: Allergic rhinitis (AR) is a common noninfectious chronic inflammatory disease of the nasal mucosa mediated by Immunoglobulin E (IgE). Currently, the diagnosis of AR mainly relies on a typical history of allergies, clinical symptoms and signs, skin prick tests, nasal provocation tests, and serum specific IgE detection. Nasal secretion cytology, as a method that directly reflects the inflammatory status in the nasal cavity, also plays a significant role in the diagnosis and treatment of AR.

Areas covered: This review summarizes and discusses the role of nasal cytology in the diagnosis and treatment of AR, based on systematically selected articles from the PubMed database, with the aim of advancing this method and its clinical application.

Expert opinion: Nasal cytology holds significant potential in revolutionizing the diagnosis and treatment of AR. Addressing the current challenges and limitations through standardization, validation studies, and integration of new technologies will pave the way for its widespread adoption and ultimately contribute to precision medicine.

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.