Expert Review of Clinical Immunology最新文献

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.

Objectives: This study aimed to assess the effectiveness and safety of intense pulsed light (IPL) therapy plus topical 0.05% cyclosporine A (CsA) eye drops to treat Sjögren's Syndrome-related dry eyes (SS-DE).

Research design and methods: In this prospective, randomized trial included, 60 individuals with SS-DE symptoms were randomized to receive topical eye drops containing either 0.1% sodium hyaluronate (Group S) or 0.05% CsA (Group C) plus IPL therapy. Before the first treatment (baseline), and at 12, 16, and 20 weeks after treatment commencement, we assessed the best corrected visual acuity (BCVA), the Ocular Surface Disease Index (OSDI) score, the Schirmer I test (SIT), noninvasive tear breakup time (NBUT), corneal fluorescein staining (CFS), meibomian gland (MG) dropout, lid margin abnormality, MG expressibility, and meibum quality.

Results: Both groups showed significant improvements in the OSDI, NBUT, CFS, MG expressibility, and meibum quality (all p < 0.05). Group C showed a greater increase in OSDI, NBUT, MG expressibility, and meibum quality (all p < 0.05). Moreover, SIT and lid margin abnormalities significantly improved in Group C (both p < 0.05), but not in Group S.

Conclusion: Treatment with 0.05% CsA eyedrops plus IPL therapy could significantly reduce the issues and physical discomfort of patients with SS-DE.

Clinical trial: Registered on 20 July 2021, with the registration number ChiCTR2100049059.

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).

Objective: This study aimed to check the expression profile of the C-X-C motif chemokine ligands (CXCLs)-C-X-C motif chemokine receptor 2 (CXCR2) axis in cervical cancer and to explore the cross-talk between cervical cancer cells and neutrophils via CXCLs-CXCR2 axis.

Methods: Available RNA-sequencing data based on bulk tissues and single-cell/nucleus RNA-sequencing data were used for bioinformatic analysis. Cervical cancer cell lines Hela and SiHa cells were utilized for in vitro and in vivo studies.

Results: Except for neutrophils, CXCR2 mRNA expression is limited in other types of cells in the cervical tumor microenvironment. CXCLs bind to CXCR2 and are mainly expressed by tumor cells. CXCL1, 2, 3, 5, 6, and 8, which are consistently associated with neutrophil infiltration, are also linked to poor prognosis. SB225002 (a CXCR2 inhibitor) treatment significantly impairs SiHa cell-induced neutrophil migration. CXCL1, CXCL2, CXCL5, or CXCL8 neutralized conditioned medium from SiHa cells have weaker recruiting effects. The conditioned medium of neutrophils from healthy donors can slow cancer cell proliferation. Conditioned medium of tumor-associated neutrophils (TANs) can drastically enhance cervical cancer cell growth in vitro and in vivo.

Conclusions: The CXCLs-CXCR2 axis is critical in neutrophil recruitment and tumor cell proliferation in the cervical cancer microenvironment.

Introduction: Fatigue and malaise are commonly associated with a wide range of medical conditions, including rheumatoid arthritis (RA). Evidence suggests that fatigue and malaise can be overwhelming for patients, yet these symptoms remain inadequately-managed, largely due to an incomplete elucidation of the underlying causes.

Areas covered: In this assessment of the published literature relating to the pathogenesis of fatigue or malaise in chronic conditions, four key mechanistic themes were identified. Each theme (inflammation, hypothalamic-pituitary-adrenal axis, dysautonomia, and monoamines) is discussed, as well as the complex network of interconnections between themes which suggests a key role for inflammatory cytokines in the development and persistence of fatigue.

Expert opinion: Fatigue is multifaceted, poorly defined, and imperfectly comprehended. Moreover, the cause and severity of fatigue may change over time, as a consequence of the natural disease course or pharmacologic treatment. This detailed synthesis of available evidence permits us to identify avenues for current treatment optimization and future research, to improve the management of fatigue and malaise in RA. Within the development pipeline, several new anti-inflammatory therapies are currently under investigation, and we anticipate that the next five years will herald much-needed progress to reduce the debilitating nature of fatigue in patients with RA.

Introduction: Hidradenitis suppurativa (HS) is an autoinflammatory skin disease with a high unmet need for effective medical management. Clinically, it is characterized by inflammatory nodules that may progress into abscesses, draining tunnels and extensive scarring, mainly affecting apocrine gland-bearing areas.

Areas covered: Treatment options include topical and systemic medications and a variety of surgical procedures. The anti-TNF-α antibody adalimumab and the anti-IL-17 secukinumab are the only two approved biologics for HS, showing moderate efficacy. HS research is a rapidly growing field, with a wide range of agents leveraging distinct mechanisms of action currently under development. Drugs targeting the IL-17 and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways are the most advanced in both ongoing and completed Phase 3 studies, promising deeper levels of response. Use of other, off-label biologics is also discussed.

Expert opinion: A therapeutic algorithm is proposed based on comorbidities and existing evidence. Patient-tailored combinations between biologics and other biologics or small molecules will hopefully allow clinicians to target most events in HS pathophysiology in a complementary way while obtaining a meaningful effect on their devastating manifestations.

Introduction: Familial Mediterranean Fever (FMF) is the most common autoinflammatory disease that has mainly been treated with colchicine since 1972. A significant portion of patients do not respond to colchicine and require further treatment, mainly IL-1β antagonists such as anakinra, canakinumab and rilonacept as IL-1β has a crucial role in pathogenesis of FMF. This review summarizes the current approach to treating FMF and discovers the pharmacological and clinical utility of IL-1 blocking agents based on accumulated evidence with a focus on anakinra.

Areas covered: This review focuses on anakinra treatment in FMF. The data obtained from case reports, case series, retrospective studies and a Phase III trial are analyzed. Safety and efficacy profiles of anakinra are discussed.

Expert opinion: Anakinra is the cheapest anti-IL-1 agent used in the treatment of colchicine-resistant FMF. It is shown to be effective and safe when used in adjunct to colchicine however its short half-life and potential to cause injection site reactions limit its use.