Expert Review of Clinical Immunology最新文献

Background: Bullous pemphigoid (BP) is a severe autoimmune sub-epidermal bullous disease. Exosomes are small extracellular vesicles secreted by most cell types. The exosomal membrane proteins are implicated in various biological and pathological pathways. This study aims to explore the potential roles of exosomes in BP pathomechanism.

Research design: We collected plasma samples from 30 BP patients and 31 healthy controls. Nanoparticle tracking analysis (NTA) was used to analyze the size and concentration of exosomes. The immunogold labelling experiment and extracellular vesicle (EV) array were performed to detect the content and distribution of exosomes.

Results: The exosomes from both the BP and control groups' plasma were successfully extracted. EV Array showed that CD63 and CD9 levels were significantly higher in the BP group than in the control group (p < 0.05). Expression levels of the BP180 NC16A and intracellular domain (ICD) were higher in the anti-BP180 positive group versus the controls (p < 0.05). The active BP group exhibits higher CD63 and BP180 ICD protein concentrations than the control or inactive BP groups (p < 0.05).

Conclusion: BP180 autoantigen fragments were expressed on the exosomal membrane in BP patients. The BP180 ICD and CD63 on exosomes could potentially be novel biomarkers for monitoring disease activity.

Introduction: Rejection remains a major obstacle to successful kidney transplantation. The complex pathophysiology of rejection depends on a fine-tuned interplay between the innate and adaptive immune systems.

Areas covered: This review provides a comprehensive analysis of the pathophysiology of rejection of kidney grafts, performed through careful selection of most relevant papers available on the topic in the PubMed database. The two types of rejection usually observed at the kidney biopsy, i.e. cellular and humoral rejection, are described with an accurate outline of the biological processes that lead to their development.

Expert opinion: The incidence of T-cell-mediated rejection is decreasing, and most cases promptly respond to appropriate immunosuppression. However, late diagnosis or incomplete response to treatment may have deleterious consequences in the long term. The main issue is represented by antibody-mediated rejection, which unsatisfactorily responds to aggressive immunosuppression, especially when diagnosed late. Prevention of acute ABMR rests on HLA-specific antibody detection prior to transplantation, adequate immunosuppression, and optimal patients' compliance. Late diagnosis and poor response to treatment inevitably lead to chronic ABMR, for which no therapies are currently available.

Objectives: There is scarce data in the literature concerning the anti-GAD65 antibodies (GAD-Abs) autoimmunity in the Omani population.

Methods: Retrospective cohort study included GAD-Abs positive patients (n = 444) presented to a tertiary referral center in Oman from January 2005 until January 2018, with a five-year follow-up to study the cancer association and mortality outcomes.

Results: Out of 444 patients, 27 patients (6.1%) showed GAD-Abs related neurological disorders. Adult age group was significantly associated with more GAD-Abs related neurological manifestations compared to pediatric and adolescents age group (p = 0.045). There was no association between the presence or absence of neurological manifestations with diabetes mellitus nor the titer level of GAD-Abs. Refractory status epilepticus and stiff person syndrome were the main causes of death in patients with neurological manifestations over five years and none of them found to have associated cancer.

Conclusion: The GAD-Abs autoimmunity represents a spectrum of neurological manifestations with variable severity and outcome among Omanis with positive GAD-Abs testing. The results of this study will serve as a platform for future studies to address the impact of GAD-Abs autoimmunity on the morbidity, mortality and treatment efficacy in the Omani population.

Introduction: Behçet disease (BD) is an inflammatory multisystem disorder of unknown etiology, believed to be triggered by infection and environmental factors in genetically predisposed individuals. The significance of understanding BD lies in its impact on global health due to its diverse clinical manifestations and geographical distribution.

Areas covered: This review discusses the epidemiology of BD, emphasizing its prevalence estimated at 10.3 (95% CI, 6.1, 17.7) per 100,000 population, with higher rates observed in regions historically linked to the Silk Route. The criteria for diagnosis are explored, focusing on clinical manifestations that guide healthcare professionals in identifying and managing BD. Additionally, the review encompasses treatment strategies, highlighting TNF-alpha inhibitors as pivotal biologics and newer agents like IL-1 inhibitors and Ustekinumab that broaden the therapeutic options for BD.

Expert opinion: Our work provides insights into the evolving landscape of treatments for BD, emphasizing the expanding role of newer agents alongside established therapies like TNF-alpha inhibitors.

Introduction: CVID is the commonest and most symptomatic primary immune deficiency of adulthood. NHLs are the most prevalent malignancies in CVID. The cross-talk between tumor cells and immune cells may be an important risk factor in lymphomagenesis.

Areas covered: The present review highlights immune cell, genetic and histopathological alterations in the CVID-associated NHLs.

Expert opinion: CVID patients exhibit some notable immune defects that may predispose to lymphomas. T/NK cell defects including reduced T cells, naïve CD4+T cells, T regs, and Th17 cells, increased CD8+T cells with reduced T cell proliferative and cytokine responses and reduced iNKT and NK cell count and cytotoxicity. B cell defects include increased transitional and CD21^low B cells, clonal IgH gene rearrangements, and increased BCMA levels. Increase in IL-9, sCD30 levels, and upregulation of BAFF-BAFFR signaling are associated with lymphomas in CVID. Increased expression of PFTK1, duplication of ORC4L, germline defects in TACI, NFKB1, and PIK3CD, and somatic mutations in NOTCH2 and MYD88 are reported in CVID-associated lymphomas. Upregulation of PD-L1-PD-1 pathway may also promote lymphomagenesis in CVID. These abnormalities need to be explored as prognostic or predictive markers of CVID-associated NHLs by large multicentric studies.

Introduction: There is a significant prevalence of chronic spontaneous urticaria (CSU) in children across the globe. Some children with CSU do not achieve disease control with first-line antihistamine treatment and may need anti-IgE therapy with omalizumab. Recently, several novel treatment options, including dupilumab and BTK inhibitors, showed promising results in the treatment of antihistamine-refractory CSU in adults. However, information regarding their use in pediatric CSU is scarce, and most data is extrapolated from adult studies.

Areas covered: The review highlights the evidence on the use of mAbs and small-molecule inhibitors in pediatric CSU and aims to bridge the knowledge gaps and highlight unmet needs.

Expert opinion: Omalizumab is approved for allergic asthma patients aged ≥6 years, and some experience with omalizumab in children with CSU at this age has been published. However, approximately 5-10% of pediatric CSU patients may show insufficient response to omalizumab, necessitating other therapies. The available information on the off-label use of biologics other than omalizumab in children is limited to case reports. No data is available for other new therapies.

Introduction: Kawasaki disease (KD) is a medium vessel vasculitis mainly affecting children below the age of 5. KD is the leading cause of acquired heart disease in developed countries. Diagnosis of KD is clinical, and there are no pathognomonic laboratory tests to confirm the diagnosis. There is a paucity of studies that have utilized proteomic approach for biomarker discovery in KD. Identification of these biomarkers may be helpful for early and more effective diagnosis and may aid in the treatment of KD.

Area covered: The present review focuses on studies that have utilized the proteomic approach in the identification of biomarkers in patients with KD. We have divided these biomarkers into three different categories: the biomarkers used for (a) assessment of risk of KD; (b) assessment of risk of coronary artery aneurysms; and (c) assessment of treatment resistance.

Expert opinion: Efforts to improve the clinical and diagnostic evaluation of KD have focused on general markers of inflammation that are not specific for KD. Identification of a proteomic-based biomarker can reliably and specifically differentiate KD from other diseases and could help in the prompt diagnosis. Comprehensive analysis of the serum proteome of patients with KD may be helpful in identifying candidate protein biomarkers.

Introduction: Bullous pemphigoid (BP) is an autoimmune bullous disease characterized by subepidermal tense blisters, accompanied by urticarial or eczema-like lesions. Circulating autoantibodies in BP patients target BP180 and BP230 at the dermal-epidermal junction. There has been a growing interest in unraveling the intricate relationship between BP and diabetes mellitus (DM), but a comprehensive review is lacking.

Areas covered: A thorough search of PubMed was conducted to identify studies concerning the association between BP and DM (1978-2023). Our findings comprehensively summarize the intricate association between BP and DM, focusing on the characteristics, potential pathomechanisms, and the influence of various antidiabetic medications on BP development.

Expert opinion: DM emerges as a prevalent comorbidity and potential risk factor for BP. New-onset DM can manifest during BP treatment, primarily due to corticosteroid therapy. Among all antidiabetic medications, dipeptidyl peptidase-IV inhibitors (DPP-4i) have the most solid association with BP onset. Other antidiabetic medications have also been reportedly associated with BP, including meglitinides, glucagon-like peptide 1 (GLP-1)-receptor agonists, and sodium-dependent glucose transporters 2 inhibitors (SGLT-2i). We suggest prescribing DPP-4i in caution for elderly DM patients with a history of autoimmune diseases.

Introduction: Eosinophilic granulomatosis with polyangiitis (EGPA) is an immune-mediated, inflammatory, multisystemic disease that is considered a form of ANCA-associated vasculitis and whose association with asthma and blood and tissue eosinophilia differentiate it from other types of vasculitis. Nevertheless, diagnosis of EGPA may be difficult or delayed not only because of the rarity of the disease, but also because other diseases can present with similar manifestations.

Areas covered: We review a series of key areas in EGPA, namely, laboratory and clinical indicators of disease, diagnosis, role of biomarkers, induction and maintenance therapy, and use of traditional and novel drugs. This narrative review was based on a thorough search of PubMed.

Expert opinion: Clinicians should be aware of the limitations of available tools for diagnosing EGPA, and more efforts should be made to identify clinical and laboratory red flags, with the purpose of achieving an early diagnosis before irreversible damage occurs. New effective therapies are available, although future research should target an approach that spares glucocorticoids, reduces the risk of flares and organ damage, and maintains long-term remission with minimum adverse effects.

Introduction: Tight junctions (TJs) and their constituent proteins play pivotal roles in cellular physiology and anatomy by establishing functional boundaries within and between neighboring cells. While the involvement of TJ proteins, such as claudins, in cancer is extensively studied, studies highlighting their interaction with immune system are still meager. Studies indicate that alterations in cytokines and immune cell populations can affect TJ proteins, compromising TJ barrier function and exacerbating pro-inflammatory conditions, potentially leading to epithelial cell malignancy. Disrupted TJs in established tumors may foster a pro-tumor immune microenvironment, facilitating tumor progression, invasion, epithelial-to-mesenchymal transition and metastasis. Although previous literature contains many studies describing the involvement of TJs in pathogenesis of malignancies their role in modulating the immune microenvironment of tumors is just beginning to be unleashed.

Areas covered: This article for the first time attempts to discern the importance of interaction between TJs and immune microenvironment in malignancies. To achieve the above aim a thorough search of databases like PubMed and Google Scholar was conducted to identify the recent and relevant articles on the topic.

Expert opinion: Breaking the vicious cycle of dysbiosis/infections/chemical/carcinogen-induced inflammation-TJ remodeling-malignancy-TJ dysregulation-more inflammation can be used as a strategy to complement the effect of immunotherapies in various malignancies.