Expert Review of Clinical Immunology最新文献

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.

Introduction: Respiratory syncytial virus (RSV) is an important pathogen in infants, children, older adults, and those with comorbidities. Mechanisms involving viral proteins appear to underlie the ability of RSV to evade and modulate host immunity. We aimed to understand virus- and host-dependent factors regulating the development and severity of RSV infection, as related to the prevention and treatment of RSV-associated disease in adults, through a systematic literature review (SLR).

Methods: An SLR was conducted to identify immune mechanisms involved in the protective response to RSV infection in adults, and responses that may contribute to the development of severe disease. Concurrent searches (MEDLINE/Embase) using embase.com identified relevant papers published between 1990 and 19 April 2023.

Results: Of 1813 records identified, 113 were selected for review. Inclusion criteria were based on relevant patient populations, outcomes, and study methodologies. RSV is common, recurrent, and associated with high morbidity and mortality in older adults and people with underlying chronic diseases. Immune responses differ between younger and older adults. The approval of effective vaccines may protect older individuals from symptomatic RSV infection.

Conclusions: We established the complexities of RSV immune response, but further research is required to fully understand anti-RSV immunology.

Introduction: Allergic rhinitis (AR) is global health concern with an increasing prevalence. Among them, pollen-induced AR (PIAR) exhibits more severe and intense symptoms, decreased quality of life, prominent local inflammation, and is thus more challenging to control. Due to the difficulties in disease control, in recent years, an increasing number of treatment methods, including pharmacotherapy, allergen-specific immunotherapy, and newly developed biologics, have focused on PIAR. It has been shown that the pollen exposure has a significant impact on the symptoms of PIAR and the efficacy of intervention. From this perspective, clinical trials for PIAR need to take full account of pollen exposure, especially when assessing efficacy.

Areas covered: This review summarized the effect of pollen exposure on PIAR, including immune responses, symptoms and clinic visits. Current definitions for the pollen season (PS) and the peak pollen season (PPS) are discussed. Based on the previous PIAR-related clinical studies and the available recommendations for clinical trial design, a detailed account of trial protocols which fully considered pollen exposure is provided.

Expert opinion: Pollen exposure has a significant impact on PIAR. With fully considering the pollen exposure in the clinical trial design for PIAR, future protocols for PIAR-related studies may be more objective and better harmonized and, therefore, comparable.

Introduction: Among the neuropsychiatric manifestations of Systemic lupus erythematosus (SLE), there are manifestations related to the peripheral nervous system (PNS). The autonomic nervous system, a subdivision of the PNS, is poorly studied in patients with SLE, and most often not recognized in clinical practice. However, it's possible that autonomic impairment is more common than we thought and many manifestations without a clear pathophysiology may be explained by autonomic impairment.

Areas covered: This review is based on selected articles from the PUBMED database that evaluated autonomic dysfunction in SLE. Also explored some common symptoms in SLE without a clearly explanation, that can be due to autonomic impairment. Finally, we propose a clinical approach to autonomic evaluation in SLE.

Expert opinion: A wide range of clinical manifestations in SLE can be attributed to autonomic dysfunction, therefore it is important to search for this diagnosis to correctly treat patients and promote a better quality of life. The long-term impact of autonomic impairment is unknown, and yet there is no biomarker that can help in the diagnosis.

Background: Vitiligo is a chronic autoimmune skin depigmenting condition. IFN-γ, TNF-α and granzyme B play key roles in vitiligo pathogenesis, some findings suggest their roles may be contradictory.

Objective: We aimed to assess IFN-γ, TNF-α and granzyme B levels in blood and skin of vitiligo patients using a meta-analysis approach. Additionally, we evaluated their association with disease activity.

Methods: A Meta-analysis was conducted using Review Manager 5.4 software. A total of 55 studies including 3,023 vitiligo patients and 2,534 controls were included in the study.

Results: Pooled results from our meta-analysis indicated significantly elevated IFN-γ protein and transcript levels in blood and skin of vitiligo patients (p < 0.05). TNF-α protein levels were also significantly increased in blood and skin of vitiligo patients (p < 0.05). IFN-γ and TNF-α levels were significantly higher in the lesional skin as compared to non-lesional skin (p < 0.05). Furthermore, elevated levels of IFN-γ and TNF-α were observed in patients with active vitiligo (p < 0.05). Additionally, our study suggested a significant increase in granzyme B levels in vitiligo patients (p < 0.05).

Conclusion: Overall, the meta-analysis suggests that IFN-γ, TNF-α and granzyme B play a crucial role in vitiligo pathogenesis and progression and may serve as potential therapeutic targets for managing the disease. The PROSPERO registration no. for meta-analysis is CRD42024620274.