Expert Review of Clinical Immunology最新文献

Introduction: Systemic sclerosis (SSc) is a connective tissue disease with heterogeneous presentation. Gastrointestinal (GI) complications of SSc are characterized by esophageal reflux, abnormal motility, and microbiome dysbiosis, which impact patient quality of life and mortality. Preventative therapeutics are lacking, with management primarily aimed at symptomatic control.

Areas covered: A broad literature review was conducted through electronic databases and references from key articles. We summarize the physiology of gastric acid production and GI motility to provide context for existing therapies, detail the current understanding of SSc-GI disease, and review GI medications studied in SSc. Finally, we explore new therapeutic options. We propose a management strategy that integrates data on drug efficacy with knowledge of disease pathophysiology, aiming to optimize future therapeutic targets.

Expert opinion: SSc-GI complications remain a challenge for patients, clinicians, and investigators alike. Management presently focuses on treating symptoms and minimizing mucosal damage. Little evidence exists to suggest immunosuppressive therapy halts progression of GI involvement or reverses damage, leaving many unanswered questions about the optimal clinical approach. Further research focused on identifying patients at risk for GI progression, and the underlying mechanism(s) that drive disease will provide opportunities to prevent long-term damage, and significantly improve patient quality of life.

Objective: This study aims to explore the relevance of anoikis in idiopathic pulmonary fibrosis (IPF) and identify associated biomarkers and signaling pathways.

Method: Unsupervised consensus cluster analysis was employed to categorize IPF patients into subtypes. We utilized Weighted Gene Co-Expression Network Analysis (WGCNA) and Protein-Protein Interaction network construction to identify anoikis-related modules and key genes. A prognostic signature was developed using Lasso and multivariate Cox regression analysis. Single-cell sequencing assessed hub gene expression in various cell types, and both cell and animal experiments confirmed IPF-related pathways.

Results: We identified two distinct anoikis-associated subtypes with differing prognoses. WGCNA revealed essential hub genes, with SPP1 being prominent in the anoikis-related signature. The anoikis-related signature is effective in determining the prognosis of patients with IPF. Single-cell sequencing highlighted significant differences in SPP1 expression, notably elevated in fibroblasts derived from IPF patients. In vivo and in vitro experiments demonstrated that SPP1 enhances fibrosis in mouse lung fibroblasts by regulating p27 through the PI3K/Akt pathway.

Conclusion: Our research demonstrates a robust prognostic signature associated with anoikis and highlights SPP1 as a pivotal regulator of the PI3K/AKT signaling pathway in pulmonary fibrosis.

Introduction: IgA nephropathy is one of the most common forms of glomerular disease. Patients with persistent proteinuria are at increased risk of progression to kidney failure. There is a significant need for safe and effective therapies to lower proteinuria in these patients. Sparsentan is a non-immunosuppressive agent that acts as a dual angiotensin and endothelin receptor antagonist. It lowers proteinuria in experimental models of glomerular disease and in affected patients.

Areas covered: This review covers the immunological and non-immunological actions of sparsentan in glomerular disease. It reviews the clinical trials that evaluated the impact of the drug in pediatric and adult patients with IgA nephropathy. It places the use of sparsentan in an overall treatment paradigm for the full spectrum of patients with IgA nephropathy including nonspecific renoprotective agents such as inhibitors of the renin-angiotensin-aldosterone axis and SGLT2 transporter and immunosuppressive drugs. The review represents a search of the current literature about the effect of the drug on normal physiology and the pathogenesis of IgA nephropathy.

Expert opinion: The safety, tolerability, and therapeutic efficacy of sparsentan have been demonstrated in long-term studies of patients with primary glomerular diseases extending over 5 years. The evidence in support of a beneficial treatment effect of sparsentan is stronger in IgAN than in FSGS. It is anticipated that sparsentan will supplant the use of ACEI or ARB as the first-line therapy to reduce proteinuria prior to the implementation of immunosuppressive agents in patients with IgA nephropathy. It may be combined with other renoprotective drugs like SGLT2 inhibitors. Practice guidelines are needed to promote safe and effective use of this new drug by nephrologists caring for patients with IgAN in all clinical settings.

Introduction: DBV712 250 µg (also referred to as Viaskin Peanut or peanut patch; Viaskin is a trademark of DBV Technologies) is an innovative approach to epicutaneous immunotherapy (EPIT). The patch-based technology system facilitates peanut protein (allergen) absorption into the intact non-vascularized epidermis to promote desensitization to peanut while limiting systemic allergen exposure.

Areas covered: Efficacy and safety in children have been evaluated in four completed phase 3 studies. Overall, the results from these studies have demonstrated the peanut patch to be superior in desensitization compared with placebo and safe for daily use over multiple years.

Expert opinion: These findings, as well as supportive evidence from phase 2 studies, confirm the potential for an effective treatment of peanut allergy in children. The purpose of this review is to summarize the safety and efficacy of the peanut patch in the treatment of peanut allergy.

Objective: Coronary artery lesions (CALs) are a major complication of Kawasaki disease (KD); however, data on CAL incidence and risk factors in recurrent KD are limited.

Methods: Ninety-seven children with recurrent KD were retrospectively enrolled from 2013 to 2022, and CAL incidence was tracked during admission, discharge, and during follow-up.

Results: Initially, 27.8% had CAL at admission and discharge, declining to 7.2% at 12 months post-discharge. Most patients (66 of 97, 68.0%) did not exhibit CAL at any of the time points, 7 cases presented CAL at all time points, indicating a persistent CAL. The remaining 20 cases presented CAL at admission but recovered at discharge or during follow-up. Notably, transient CALs had presented at discharge, or during the follow-up, but finally resolved at 12 months after discharge. Notably, prior IVIG resistance and increased prothrombin time seemed associated with CAL in recurrent KD, suggesting they could help identify patients needing close monitoring.

Conclusion: The study highlights decreasing CAL incidence over time in recurrent KD but with diverse patterns, emphasizing the importance of monitoring and further investigations to confirm these findings.

Objectives: We aimed to determine the discriminative values of pro-inflammatory cytokines to distinguish spondyloarthritis patients from healthy subjects and to assess the association between these cytokines and spondyloarthritis characteristics.

Methods: We conducted a case-control study, including 144 subjects matched for age and sex: 72 spondyloarthritis patients(G1) and 72 controls (G2). The disease activity was assessed using ASDAS-CRP and BASDAI. Structural damage was assessed using BASRI. The levels of interleukin (IL) IL-1, IL-6, IL-8, IL-17, IL-23, and tumor necrosis factor α(TNFα) were measured.

Results: Each group included 57 men. The mean age was 44.84 ± 13.42 years. Except for IL-8, all cytokine levels were significantly higher in patients compared to controls (IL-1: p = 0.05, IL-6: p = 0.021, TNFα: p = 0.039, IL-17 and IL-23: p < 0.001). Cutoff values of IL-17 and IL-23 distinguishing patients in G1 from those in G2 were 17.6 and 7.96 pg/mL, respectively. TNFα level correlated to BASDAI (p = 0.029) and BASRI (p = 0.002). Multivariate analysis showed that structural damage was associated with the male gender (p = 0.017), longer disease duration (p = 0.038), and high disease activity (p = 0.044). Disease activity was associated with longer disease duration (p = 0.012) and increased IL-6 levels (p = 0.05).

Conclusion: Our study showed that IL-17 was the ablest to distinguish between spondyloarthritis patients and controls, suggesting that IL-17 may be helpful for the diagnosis of spondyloarthritis.

Objective: In this study, we explored the expression of transcription factors, cytokines, and co-stimulatory molecules within the helper T (Th) cell subsets (Th1, Th2, Th17 and Treg) of patients with hypomorphic DCLRE1C gene mutations.

Methods: The study comprised eight patients and five controls. Transcription factor and cytokine expressions of Th subsets and co-stimulatory molecules were investigated by qPCR and flow cytometric following T cell stimulation. The findings were compared between patients (non-HSCT) and with hematopoietic stem cell transplantation (HSCT).

Results: Flow cytometric analyses; while the Treg rate was significantly lower in non-HSCT than in controls (p = 0.010), the IFN-γ rate was significantly higher in patients than in the control and HSCT groups (p = 0.016, p = 0.022 respectively). Co-stimulatory molecule expressions were significantly lower in non-HSCT than in control (p < 0.001), and there was a significant improvement after HSCT. Post-stimulation qPCR analysis, significant changes were detected in non-HSCT/control, non-HSCT/HSCT and HSCT/control comparisons.

Conclusions: Our study is the first study to molecularly investigate Th cell subsets in hypomorphic DCLRE1C patients. It was determined that abnormalities in Th cell subsets still persisted despite HSCT. There are still many conditions to be explained in these patients, and we believe that our study may shed light on future studies.

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease with systemic manifestations. Although the success of immune modulatory drug therapy is considerable, about 40% of patients do not respond to treatment. Mesenchymal stromal/stem cells (MSCs) have been demonstrated to have therapeutic potential for inflammatory diseases.

Areas covered: This review provides an update on RA disease and on pre-clinical and clinical studies using MSCs from bone marrow, umbilical cord, adipose tissue, and dental pulp, to regulate the immune response. Moreover, the clinical use, safety, limitations, and future perspective of MSCs in RA are discussed. Using the PubMed database and ClincalTrials.gov, peer-reviewed full-text papers, abstracts and clinical trials were identified from 1985 through to April 2023.

Expert opinion: MSCs demonstrated a satisfactory safety profile and potential for clinical efficacy. However, it is mandatory to deepen the investigations on how MSCs affect the proinflammatory deregulated RA patients' cells. MSCs are potentially good candidates for severe RA patients not responding to conventional therapies but a long-term follow-up after stem cells treatment and standardized protocols are needed. Future research should focus on well-designed multicenter randomized clinical trials with adequate sample sizes and properly selected patients satisfying RA criteria for a valid efficacy evaluation.

Introduction: Allergic contact dermatitis (ACD) is a common cutaneous inflammatory skin disorder that is diagnosed via epicutaneous patch testing (PT). ACD may also coexist with other systemic inflammatory conditions such as atopic dermatitis and psoriasis. Many of the treatments used to manage severe ACD, along with other systemic conditions, interact with and suppress the immune system, thereby potentially interfering with the mechanism of PT. There is uncertainty in the literature regarding the effects of immunosuppression on the results of PT.

Methods: A comprehensive literature review was conducted using PubMed and Google Scholar to identify articles relevant to the topic of this review. Only articles available in English were included.

Areas covered: This review discusses the impact of immunomodulating therapies on the results of PT. We summarize the available evidence and provide updated recommendations for several immunomodulating drugs commonly used in patients undergoing PT.

Expert opinion: In general, the results of PT are most reliable when performed without immunosuppression. If this is not feasible, it is best to have patients on as low a dose of immunosuppression as possible, but it may not be necessary to stop or change an immunomodulating drug prior to PT.

Introduction: Targeting IL-17A using Secukinumab, a humanized monoclonal immunoglobulin G1 (IgG1)/κ against IL-17A is a therapeutic option for immune-mediated disorders such as psoriasis and ankylosing spondylitis. The US Food and Drug Administration and the European Medicines Agency have approved it for the treatment of moderate to severe plaque psoriasis, active psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondylarthritis. Recently it has also been approved for use in children with severe plaque psoriasis, active psoriatic arthritis, and enthesitis-related arthritis.

Areas covered: This review focuses on the role of Secukinumab in the management of children and adolescents with enthesitis-related arthritis and psoriatic arthritis. We discuss the salient findings of pivotal RCTs and other studies supporting the use of Secukinumab in adults and children, in particular, focusing on its safety and efficacy.

Expert opinion: Secukinumab is a therapeutic target for psoriasis, psoriatic arthritis, and spondyloarthropathies in both adults and children. No major safety signals are observed with its use in short-term follow-up. Thus far, Secukinumab has not been found to significantly increase the risk of tuberculosis (TB).