Expert Review of Clinical Immunology最新文献

Introduction: Acute graft versus host disease (aGVHD) is a potentially lethal complication after allogeneic stem cell transplantation. Biomarkers are used to estimate the risk of aGVHD and evaluate response to treatment. The most widely used biomarkers are systemic levels of various protein mediators involved in immunoregulation or reflecting tissue damage. However, systemic levels of other molecular markers such as nucleic acids or metabolites, levels of immunocompetent cells or endothelial cell markers may also be useful biomarkers in aGVHD.

Areas covered: This review is based on selected articles from the PubMed database. We review and discuss the scientific basis for further studies to evaluate nucleic acids, metabolites, circulating immunocompetent cell subsets or endothelial markers as biomarkers in aGVHD.

Expert opinion: A wide range of interacting and communicating cells are involved in the complex pathogenesis of aGVHD. Both nucleic acids and metabolites function as soluble mediators involved in communication between various subsets of immunocompetent cells and between immunocompetent cells and other neighboring cells. Clinical and experimental studies suggest that both neutrophils, monocytes, and endothelial cells are involved in the early stages of aGVHD pathogenesis. In our opinion, the possible clinical use of these molecular and cellular biomarkers warrants further investigation.

Introduction: The present paper aimed to conduct an updated systematic review and meta-analysis to evaluate the safety and efficacy of crisaborole, delgocitinib, and ruxolitinib in treating mild-to-moderate atopic dermatitis (AD).

Methods: MEDLINE and Google Scholar databases were utilized to search articles published during the years 2015-2024. The review was limited to randomized controlled studies that measured specific outcomes for safety and efficacy aspects, including adverse events (AEs) or treatment-emergent adverse events (TEAEs) to evaluate safety and Investigator's static global assessment (ISGA) or improvement of at least 75% of Eczema Area and Severity Index (EASI-75) to evaluate efficacy.

Results: The review included 17 articles in the analysis. The safety odds ratios (ORs) among participants using crisaborole, delgocitinib, and ruxolitinib were 1.14, 95% CI [0.97-1.36], 1.18, 95% CI [0.84-1.67], and 0.72, 95% CI [0.55-0.94], respectively, when compared to control groups. The three studied topical AD treatments were found to be significantly more effective compared to control groups (crisaborole, OR = 1.78, 95% CI [1.51-2.10], delgocitinib, OR = 6.34, 95% CI [3.57-11.27], and ruxolitinib, OR = 7.30, 95% CI [5.10-10.44]).

Conclusion: Delgocitinib and ruxolitinib demonstrated favorable safety and effectiveness profiles across various age cohorts, whereas crisaborole raised concerns over its safety and efficacy, particularly in children.

Background: This study analyzed the clinical utility of serum adipocytokines and inflammatory cytokines in gestational diabetes mellitus (GDM) and developed a quantitative nomogram prediction model.

Research design & methods: General data were collected. Fasting venous blood was taken and levels of fasting plasma glucose (FPG), serum adipocytokines, and inflammatory cytokines were assessed. The main risk factors for GDM were analyzed by implementing univariate and multivariate logistic regression analysis. The weights of the main risk factors were assigned, and the nomogram prediction model for GDM was developed by R software. The efficacy of the nomogram model for GDM prediction was measured and analyzed by the receiver operating characteristic (ROC) curve and calibration curve.

Results: The observation group possessed a higher proportion of family history of diabetes, raised FPG, LEP, Visfatin, hs-CRP, IL-6, and TNF-α contents, and lower ADP contents (all p < 0.05). Multivariate logistic regression analysis displayed that LEP, ADP, and IL-6 were the main risk factors for GDM (p < 0.05). Calibration curve was basically consistent with the original curve, suggesting good accuracy.

Conclusion: Serum adipocytokines and inflammatory cytokines were the main risk factors for GDM. Developing a nomogram model can facilitate early diagnosis of GDM by physicians, allowing for timely interventions.

Introduction: In recent years, immunotherapy has shown significant therapeutic potential in patients with advanced tumors. However, only a small number of individuals benefit, mainly due to the tumor microenvironment (TME), which provides conditions for the development of tumors. Macrophages in TME, known as tumor-associated macrophages (TAM), are mainly divided into M1 anti-tumor and M2 pro-tumor phenotypes, which play a regulatory role in various stages of tumorigenesis, promote tumorigenesis and metastasis, and cause immunotherapy resistance.

Areas covered: This review focuses on research strategies and preclinical/clinical research progress in translating TAM into antitumor phenotype by referring to the PubMed database for five years. These include small molecule chemotherapy drug development, metabolic regulation, gene editing, physical stimulation, nanotechnology-mediated combination therapy strategies, and chimeric antigen receptor-based immunotherapy.

Expert opinion: It is necessary to explore the surface-specific receptors and cell signaling pathways of TAM further to improve the specificity and targeting of drugs and to strengthen research in the field of probes that can monitor changes in TAM in real time. In addition, the physical stimulation polarization strategy has the advantages of being noninvasive, economical, and stable and will have excellent clinical transformation value in the future.

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.

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: 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.

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: 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.