Expert Review of Clinical Immunology最新文献

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver comorbidity in patients with inflammatory bowel disease (IBD).

Areas covered: This paper outlines common pathophysiological aspects related to MASLD and IBD; describes the epidemiological clues associated with both diseases; analyzes risk factors contributing to MASLD appearance and progression in IBD patients; reviews data on clinical consequences for this population; and provides advice on the management of patients with both conditions.

Expert opinion: IBD itself, especially Crohn's disease, is a risk factor for MASLD and its progression to liver cirrhosis, independent of other cardiometabolic risk factors. Intestine-dependent mechanisms which contribute to MASLD in IBD and interplay with classic metabolic factors include sarcopenia, disease phenotype, duration, and activity. Changes in microbiota also contribute to deregulating the gut-liver axis in these conditions. By contrast, IBD therapies do not seem to play a relevant role in the risk of developing MASLD; and the potential of biologics and novel small molecules on liver changes requires further investigation. MASLD increases comorbidities, impairs clinical outcomes, and increases mortality in IBD patients; therefore, early detection of MASLD is a priority in IBD populations. Individualized and integrative management of both MASLD and IBD is required to improve results.

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is characterized by persistent respiratory symptoms and airflow limitation. A subset of patients exhibits eosinophilic inflammation, which has been shown to impact disease severity and exacerbation frequency.

Areas covered: This review aims to provide an update on the role of eosinophils in COPD and the efficacy of biologics targeting inflammation. Furthermore, we will explore eosinophilia as a biomarker for COPD outcomes. The findings highlight the potential of biologics in managing COPD. We conducted a review of the English-language literature from the beginning of the databases reviewed through April 2025.

Expert opinion: In COPD there is a close interplay between inflammation, lung damage and multimorbidities, mechanisms that determine a lower efficacy of biologics. Patients currently eligible for biologics are only the subpopulation with eosinophilic airway inflammation, but biologics that target broad-acting epithelial cytokines might have a greater efficacy in a complex disease such as COPD. This is because their mechanism of action is not limited to modulation of eosinophilic inflammation alone but to multiple driver pathways. Looking forward, there is an urgent need to identify new biomarkers for better patient selection to improve the impact of biologics, which is still not yet fully satisfactory.

Introduction: Some genetic polymorphisms are associated with the risk of stroke, although the individual contribution of such polymorphisms is considered modest.

Aims: To evaluate the frequency of single nucleotide polymorphisms (SNPs) in genes encoding proinflammatory cytokines and coagulation factors in stroke patients, the relationships between the serum levels of the cytokines analyzed with stroke subtypes and prognosis.

Material and methods: A retrospective, cross-sectional, observational, analytical, case-control study. We performed genetic analysis to evaluate various genetic polymorphisms and analyzed cytokine levels at admission.

Results: 429 patients with ischemic stroke and 195 control subjects without ischemic stroke. Patients with CEI subtype showed significantly higher levels of all the cytokines analyzed, namely, IL-10, TNF-alpha, and IL-6. Logistic regression analysis revealed that higher TNF-α (alpha), IL-6, and IL-1 β levels were significantly associated with the LAAS and CEI subtypes. TNF-α, IL-1, and IL-6 levels were significantly higher in patients with recurrent stroke at follow-up. Of the three polymorphisms in the gene encoding PTSG2, the haplotypes rs6275 and rs20417 showed a different distribution between patients and controls.

Discussion: The reported association between ischemic stroke and immunoinflammatory variables agrees with previously reported associations between some proinflammatory and prothrombotic polymorphisms and the risk of ischemic stroke.

Introduction: Phosphoinositide-3-kinase δ (PI3Kδ) is a critical regulator of cellular processes, predominantly within the immune system, and its dysregulation is implicated in inborn errors of immunity, including Activated PI3 Kinase Delta Syndrome (APDS), and various malignancies, including hematological and solid tumors. Given PI3Kδ's predominant expression in leukocytes, its aberrant activation not only promotes tumor growth but also enables immune evasion, underscoring its importance as an 'immune-check pathway,' especially in immune-rich tumor microenvironments.

Areas covered: This review examines the oncogenic role of PI3Kδ signaling, emphasizing its contribution to immune evasion, tumor proliferation, survival, and metastasis across different cancers. A bibliographic search was conducted in PubMed, Science Direct, MEDES and SciELO using specific criteria for articles published until 2023.

Expert opinion: PI3Kδ signaling can be conceptualized as an immune check pathway, reinforcing its potential as a therapeutic cancer target. Recent clinical trials using PI3Kδ inhibitors have shown efficacy across various cancers (hematological, breast, gynecologic, and digestive cancers), suggesting their applicability beyond APDS and primary malignancies. This approach could prevent cancer-linked immunodeficiency, providing dual therapeutic and prophylactic benefits. Future research should explore PI3Kδ inhibitors as a comprehensive strategy for managing cancer progression and associated immune dysfunction, ultimately improving patient outcomes.

Introduction: Multiple sclerosis (MS) is the most recognized CNS autoimmune demyelinating disease, characterized by neuroinflammation, myelin loss, and axonal damage. Due to clinical overlap with several disorders such as systemic autoimmune diseases (SADs), which can closely resemble MS, the diagnostic process can be challenging. SADs with CNS involvement can present with neurological symptoms such as transverse myelitis, optic neuritis, and white matter lesions. This diagnostic uncertainty contributes to a significant rate of misdiagnosis which can lead to improper treatment, worsening symptoms, and increasing disability.

Areas covered: In this review, we discuss the physiology of myelin in the CNS, the pathophysiology of MS and other immune-mediated demyelinating diseases that can mimic MS. We also discuss similar presentations between MS and MS-like clinical entities, and their appropriate treatment regimes.

Expert opinion: SADs and other clinical entities are key MS mimickers, significantly complicating diagnosis at a first neurological episode. Careful clinical evaluation, imaging, and exclusion of alternative diagnoses are crucial to avoid misdiagnosis. Understanding the subtle distinctions between MS and SADs and looking out for, and further investigating atypical presentations, is vital for ensuring accurate diagnosis and proper treatment, thereby improving patient outcomes and reducing unnecessary disability.

Introduction: Asthma and type 2 diabetes mellitus (T2DM) are chronic diseases with a significant global health burden. Recent studies have highlighted the complex relationship between these two diseases, particularly regarding their pharmacological management.

Areas covered: This review discusses the mechanisms linking asthma and T2DM and the interactions between asthma and T2DM therapies, highlighting the potential clinical implications. We examine the effects of asthma medications on glycemic control and diabetes management and review the effects of commonly used T2DM medications on outcomes in patients with asthma.

Expert opinion: Effectively managing asthma and T2DM requires an understanding of the beneficial and adverse effects of asthma drugs on glucose metabolism. It is also essential to consider the potential benefits of diabetes treatments on respiratory health and the impact of obesity on both diseases. Such knowledge can facilitate the optimization of drug plans and the minimization of adverse effects, while exploiting potential synergies between treatments for these diseases. However, to improve understanding of the complex mechanisms underlying the interaction between these chronic diseases, further research using a comprehensive approach that includes inflammatory pathways, metabolic factors, therapeutic interventions, gender differences, and lifestyle influences is needed.

Introduction: Vitiligo is a chronic autoimmune skin disorder characterized by the loss of melanocytes, leading to depigmented patches on the skin and mucous membranes. Its increasing prevalence and impact on patients' quality of life highlight the need for updated therapeutic strategies.

Areas covered: This review discusses recent advances in the understanding of vitiligo pathogenesis, focusing on genetic predisposition, environmental triggers, and immune dysregulation-particularly the role of autoreactive CD8+ T cells and inflammatory cytokines such as IFN-γ. The literature search included recent clinical trials and emerging therapies. Novel approaches, including JAK inhibitors (e.g. povorcitinib, upadacitinib) and monoclonal antibodies (e.g. anifrolumab), are evaluated for their efficacy and safety based on phase II and III clinical trial data.

Expert opinion: Targeted therapies that address immune mechanisms and oxidative stress represent promising advances in vitiligo management and may substantially improve patient outcomes in the near future.

Background: The protective effects of inactivated COVID-19 vaccines against SARS-CoV-2-associated semen impairment remain underexplored. We aimed to investigate the association between BBIBP-CorV vaccination and semen quality in males recovering from SARS-CoV-2 infection.

Research design and methods: This single-center retrospective cohort study included males recovering from SARS-CoV-2 infection at a tertiary hospital in Urumqi, China (February-May 2023). Participants were categorized into long-term (> 90 days) and short-term (≤ 90 days) effects groups based on the interval between semen collection and their most recent SARS-CoV-2 infection. The study assessed the association between different doses of BBIBP-CorV vaccination and semen quality in both groups.

Results: A total of 1496 participants were recruited for the short-term (n = 307) and long-term effect groups (n = 1189). Participants had a median age of 32 (IQR: 30, 35) years. Compared to unvaccinated controls, 2-dose and 3-dose recipients showed reduced risk of semen quality impairment in short-term, with adjusted relative risk (RR) of 0.945 (95% CI 0.918, 0.973) and 0.965 (95% CI 0.937, 0.993), respectively. No significant results were found for long-term effect groups.

Conclusion: Inactivated COVID-19 vaccination may protect against semen quality impairment in males recovering from SARS-CoV-2 Omicron infection within 90 days, particularly in semen volume and sperm progressive motility.

Introduction: Dupilumab is a monoclonal antibody that inhibits the IL-4 receptor alpha, preventing the binding of IL-4 and IL-13 and the subsequent signal transduction. Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common form of cutaneous T-cell lymphoma (CTCL). Several cases of MF have been reported following the initiation of dupilumab in patients previously diagnosed with atopic dermatitis.

Areas covered: This article is a narrative review of the current state of knowledge regarding the correlation between dupilumab and the development of CTCL. Clinical studies on this topic are reviewed, with a particular focus on the pathogenetic theories proposed to date. Finally, we present a new theory, previously undescribed, regarding the potential role of the cytokine microenvironment in triggering CTCL in patients treated with dupilumab.

Expert opinion: Dupilumab could unmask CTCLs by inhibiting IL-4. In fact, a recent study observed that IL-4 plays a key role in maintaining the 'equilibrium phase' between tumor and microenvironment cells. Disruption of this balance could promote the escape of tumor cells and lead to the unmasking of CTCLs.

Objectives: Endothelial dysfunction is associated with increased cardiovascular risk in individuals with autoimmune diseases. This systematic review and meta-analysis included studies assessing endothelial function with functional methods in children with rheumatic diseases versus controls.

Methods: Literature search involved PubMed and Scopus databases (from inception to February 2024) and manual reference screening. Studies assessing endothelial function by all available functional methods were eligible. Study quality was evaluated via Newcastle-Ottawa scale.

Results: Twenty-four studies (880 children with rheumatic diseases, 784 controls) were included in meta-analysis. Pooled analysis showed significantly impaired endothelial function in patients versus controls (SMD: -0.74, 95%CI -1.10 to -0.39) but with high heterogeneity (I² = 91%, p < 0.001); sensitivity analysis including only high-quality studies confirmed this finding (SMD: -0.83, 95%CI -1.20 to -0.46). In subgroup analyses according to type of rheumatic disease, significantly impaired endothelial function was showed for patients with juvenile idiopathic arthritis (SMD: -1.05, 95%CI -1.84 to -0.25), vasculitis (SMD: -0.74, 95%CI -1.11 to -0.37) and juvenile systemic sclerosis (SMD -2.48, 95%CI -4.34 to -0.61).

Conclusions: Children with rheumatic diseases show impaired endothelial function. Future studies are needed to elucidate whether endothelial dysfunction is involved in high cardiovascular risk of these patients.

Prospero registration number: CRD42023413799.