Expert Review of Clinical Immunology最新文献

Introduction: Severe combined immunodeficiency (SCID) is an inborn error of immunity that is fatal without hematopoietic cell transplantation (HCT) or gene therapy (GT). Survival outcomes have improved, largely due to implementation of SCID newborn screening. A better understanding of the long-term outcomes and late effects to address critical aspects of monitoring immune and general health life-long is needed.

Areas covered: In a comprehensive review of PubMed indexed articles with publication dates 2008-2024 we describe the current knowledge of chronic and late effects (CLE) of HCT survivors for SCID as well as the role of GT and advances for specific SCID genotypes. We review factors affecting the development of CLE including disease related factors (genotype, trigger for diagnosis and presence of infection prior to HCT), transplant related factors (type of donor, conditioning regimen, immune reconstitution and graft versus host disease (GVHD) and describe causes and factors associated with higher risk for late mortality in this unique population. We further describe monitoring and potential therapeutic strategies for management of common CLE in this patient population.

Expert opinion: Ongoing research efforts are needed to better describe CLE in survivors, to develop prospective clinical trials aimed at mitigating these CLE, and developing genotype-based approaches for management and follow-up of these patients.

Introduction: Allergen immunotherapy (AIT) is the only disease-modifying treatment for patients with IgE-mediated allergic diseases. Successful AIT can induce long-term immune tolerance to the common allergen, which provides clinical benefits for years after discontinuation. The cytokine interleukin (IL)-10, as a key anti-inflammatory mediator with strong immunoregulatory functions, has drawn increasing attention over the past decades.

Areas covered: After an extensive search of PubMed, EMBASE, and Web of Science databases, covering articles published from 1989 to 2024, our review aims to emphasize the key common information from previous reviews on the crucial involvement of IL-10 in allergen immunotherapy (AIT) induced immunological tolerance. In this review, we discuss the regulation of IL-10 expression and the molecular pathways associated with IL-10 function. We also further summarize mechanisms of immune tolerance induced by AIT, especially the indispensable role of IL-10 in AIT.

Expert opinion: IL-10 plays an indispensable role in immune tolerance induced by AIT. Understanding the importance of the role of IL-10 in AIT would help us comprehend the mechanisms thoroughly and develop targeted therapeutics for allergic diseases.

Introduction: Kawasaki disease [KD] is a systemic disorder characterized by acute febrile illness due to widespread medium-vessel vasculitis, mainly affecting children. Despite the ongoing advanced research into the disease pathophysiology and molecular mechanisms, the exact etiopathogenesis of KD is still an enigma. Recently, single-cell RNA sequencing [scRNA-seq], has been utilized to elucidate the pathophysiology of KD at a resolution higher than that of previous methods.

Area covered: In the present article, we re-emphasize the pivotal role of this high-resolution technique, scRNA-seq, in the characterization of immune cell transcriptomic profile and signaling/response pathways in KD and explore the diagnostic, prognostic, and therapeutic potential of this new technique in KD. Using combinations of the search phrases 'KD, scRNA-seq, CAA, childhood vasculitis' a literature search was carried out on Scopus, Google Scholar, and PubMed until the beginning of 2024.

Expert opinion: scRNA-seq presents a transformative tool for dissecting KD at the cellular level. By revealing rare cell populations, gene expression alterations, and disease-specific pathways, scRNA-seq aids in understanding the intricacies of KD pathogenesis. This review will provide new insights into pathogenesis of KD and the field of applications of scRNA-seq in personalized therapeutics for KD in the future.

Introduction: Besides cytokine release syndromes (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), immune effector cell-associated HLH-like syndrome (IEC-HS) is increasingly recognized across CAR-T recipients. This emergent and fatal syndrome is difficult to separate from other disorders during the early phase, and urgently requires more integrated diagnostic and therapeutic frameworks.

Areas covered: Existing literature has pointed out the potential role of unbridled proliferation of cytotoxic T lymphocytes, lymphopenia of natural killing cells, and hypercytokinemia in triggering the IEC-HS. The onset time of IEC-HS usually overlaps with CRS or be delayed from CRS. Clinical features include hyperferritinemia, hepatic and renal dysfunctions, cytopenias, coagulopathy, and hemophagocytosis. Multiple diagnostic criteria are based predominantly on ferritin elevation and prerequisite CRS. Corticosteroids are the cornerstone for IEC-HS treatment, while cytokine-targeted agents and pathway inhibitors offer great promise in alleviating IEC-HS syndromes.

Expert opinions: Several controversial predisposing factors of IEC-HS like disease burden should be further investigated. Futures research is anticipated to identify the real-time biomarkers, as well as develop a more sophisticated grading and management network.

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.