Expert Review of Clinical Immunology最新文献

Objective: Epigenetic modifications, particularly deoxyribonucleic acid (DNA) methylation, regulate the expression of immune-mediated factors. This study aimed to investigate the methylation landscape of the interleukin-10 (IL10) gene in Graves' disease (GD).

Methods: This study quantitatively profiled DNA methylation levels within the IL-10 gene using peripheral blood samples from GD patients and healthy controls. Machine learning models were constructed based on CpG methylation features to classify disease status. Furthermore, correlation between specific CpG sites methylation and clinical indicators were analyzed.

Results: This study enrolled 60 patients diagnosed with GD and 51 healthy controls. Methylation analysis revealed significantly elevated methylation at multiple IL-10 CpG sites in the GD group compared to the healthy controls (p < 0.01), forming a hypermethylated cluster. Interestingly, the newly-diagnosed GD (NGD) group also showed higher methylation at specific sites compared to the recurrent GD (RGD) group. Correlation analysis showed that methylation at chr1_206947188_R and chr1_206947135_R were positively correlated with FT3 and TRAb levels, indicating that site-specific methylation changes were associated with disease severity and immune activity in GD.

Conclusions: Our findings highlight distinct methylation patterns of the IL-10 gene in GD, with specific CpG sites carrying potential implications for disease diagnosis, stratification, and monitoring.

Introduction: Primary antibody deficiencies (PADs), especially common variable immunodeficiency (CVID), are clinically significant inborn errors of immunity due to complex phenotypes and long-term complications. This review provides an updated overview of pulmonary and gastrointestinal manifestations in PADs, focusing on CVID.

Areas covered: We conducted a structured literature review of original articles, reviews, and guidelines from the last 10 years, using databases such as PubMed and Scopus. The focus was on immunopathogenesis, clinical features, and treatment of noninfectious pulmonary and gastrointestinal complications in CVID. Key shared immunological pathways include B- and T-cell dysregulation, cytokine-driven inflammation, and microbiota alterations.

Expert opinion: Early recognition of noninfectious complications in CVID is vital to prevent organ damage and improve outcomes. A multidisciplinary, personalized approach involving genetic, immunologic, and microbiologic assessments and specialists including pathologists, pulmonologists, and gastroenterologists is essential, considering the pulmonary-gastrointestinal axis's role in mucosal immune dysfunction and systemic immune dysregulation.

Introduction: Spondyloarthritis (SpA) includes a group of chronic inflammatory disorders affecting the axial skeleton and/or peripheral joints. The Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway is pivotal in cytokine-mediated signaling, contributing to SpA pathogenesis.

Areas covered: Cytokine inhibitors were the first biological therapies used in SpA. However, not all patients responded to this treatment. In this setting, Janus Kinase inhibitors (JAKi) have emerged as a promising option for SpA treatment. They act on JAK family members regulating many cytokine signaling pathways involved. Clinical trials have shown significant efficacy for the whole spectrum of SpA phenotypes. However, side effects have emerged and questions arise about their safety profile. This review explores the role of JAK-STAT pathway in SpA, focusing on its involvement in cytokine signaling and immune response regulation, its efficacy, and safety of JAKi. Thus, we searched the relevant literature in PubMed and Scopus from January 2016 until January 2025.

Expert opinion: JAKi are useful in the treatment of SpA and are recommended by international authorities in patients suffering from SpA. Despite the promising results, ongoing research is essential to assess the benefit-risk profile of JAKi in SpA.

Introduction: The demographic increase, environmental concerns, and heightened awareness about health have led Western countries to consider edible sources previously overlooked. The novelty of these sources implies a scarce knowledge about their allergenicity.

Areas covered: This review has the purpose of offering an arranged view about the allergenicity of different categories of novel foods, such as edible insects, new plant-based foods, and microalgae, by exploring cross-reactivity and common traits with other food allergies but also specific peculiarities. A particular regard is reserved for the framework in Western countries.

Expert opinion: Increasing efforts have been directed in the last years to identify dangerous cross-reactive allergens in novel foods, i.e. tropomyosin. On the other hand, eventual primary sensitizations should also be considered, especially for idiopathic anaphylaxis. In view of the partial knowledge about the allergenic potential of the novel sources, the education of the patient on this topic (particularly those with known food allergies), and an appropriate labeling of product's packages may reveal helpful to minimize the risk.

Introduction: Inborn errors of immunity (IEI) often manifest through alterations in T and B lymphocyte subsets, complicating early diagnosis and management; this review aims to synthesize current knowledge on lymphocyte subgroup dynamics in combined immunodeficiencies (CID) and related disorders.

Areas covered: We surveyed peer-reviewed literature focusing on flow cytometric profiling of T and B cell subpopulations in IEI, including both syndromic and non-syndromic presentations. Key studies were identified through systematic searches of PubMed and Embase between 2000 and 2024, emphasizing quantitative and qualitative changes in naive, central memory, effector memory, and regulatory subsets. Data extraction prioritized correlations between immunophenotypic patterns and genetic defects, clinical phenotypes, and therapeutic interventions.

Expert opinion: Detailed immunophenotyping holds transformative potential to expedite IEI diagnosis and inform individualized treatment strategies. However, widespread implementation faces barriers such as inconsistent assay standardization, limited access to high-dimensional flow cytometry in resource-constrained settings, and incomplete genotype-phenotype mapping. Future research should integrate multi-omic profiling and machine learning to refine diagnostic algorithms, enabling earlier therapeutic interventions - including targeted biologics, gene therapy, and optimized hematopoietic stem cell transplantation protocols - to improve patient outcomes.

Background: Endogenous retrovirus group E member 1 (EVA1A) is expressed in various normal tissues and plays a role in tumor development. However, its function in esophageal squamous cell carcinoma (ESCC) and immune regulation remains unclear.

Research design and methods: Bioinformatics, clinical samples, and in vivo/in vitro experiments were used to evaluate EVA1A expression and function. A co-culture system with CD8⁺ T cells, as well as a xenograft mouse model, was established. CD8⁺ T cell activity, glycolysis markers, lactate levels, and PLAU expression were assessed through flow cytometry, quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent (ELISA), lactate dehydrogenase (LDH) assays, and chromatin immunoprecipitation (ChIP).

Results: EVA1A was upregulated in ESCC and negatively correlated with CD8⁺ T cell infiltration. EVA1A knockdown suppressed tumor growth and immune escape by reducing glycolysis and lactate production. Lactate promoted histone H4K12la lactylation, enhancing plasminogen activator-urokinase (PLAU) expression. PLAU overexpression reversed CD8⁺ T cell activation induced by EVA1A silencing.

Conclusion: High EVA1A expression enhances glycolysis in ESCC, and the resulting lactate further induces H4K12la lactylation and promotes PLAU expression. This inhibits the anti-tumor activity of CD8⁺ T cells, suggesting that EVA1A has potential as a therapeutic target for ESCC.

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.