Expert Review of Clinical Immunology最新文献

Introduction: Allergic rhinitis (AR) is global health concern with an increasing prevalence. Among them, pollen-induced AR (PIAR) exhibits more severe and intense symptoms, decreased quality of life, prominent local inflammation, and is thus more challenging to control. Due to the difficulties in disease control, in recent years, an increasing number of treatment methods, including pharmacotherapy, allergen-specific immunotherapy, and newly developed biologics, have focused on PIAR. It has been shown that the pollen exposure has a significant impact on the symptoms of PIAR and the efficacy of intervention. From this perspective, clinical trials for PIAR need to take full account of pollen exposure, especially when assessing efficacy.

Areas covered: This review summarized the effect of pollen exposure on PIAR, including immune responses, symptoms and clinic visits. Current definitions for the pollen season (PS) and the peak pollen season (PPS) are discussed. Based on the previous PIAR-related clinical studies and the available recommendations for clinical trial design, a detailed account of trial protocols which fully considered pollen exposure is provided.

Expert opinion: Pollen exposure has a significant impact on PIAR. With fully considering the pollen exposure in the clinical trial design for PIAR, future protocols for PIAR-related studies may be more objective and better harmonized and, therefore, comparable.

Introduction: Among the neuropsychiatric manifestations of Systemic lupus erythematosus (SLE), there are manifestations related to the peripheral nervous system (PNS). The autonomic nervous system, a subdivision of the PNS, is poorly studied in patients with SLE, and most often not recognized in clinical practice. However, it's possible that autonomic impairment is more common than we thought and many manifestations without a clear pathophysiology may be explained by autonomic impairment.

Areas covered: This review is based on selected articles from the PUBMED database that evaluated autonomic dysfunction in SLE. Also explored some common symptoms in SLE without a clearly explanation, that can be due to autonomic impairment. Finally, we propose a clinical approach to autonomic evaluation in SLE.

Expert opinion: A wide range of clinical manifestations in SLE can be attributed to autonomic dysfunction, therefore it is important to search for this diagnosis to correctly treat patients and promote a better quality of life. The long-term impact of autonomic impairment is unknown, and yet there is no biomarker that can help in the diagnosis.

Background: Vitiligo is a chronic autoimmune skin depigmenting condition. IFN-γ, TNF-α and granzyme B play key roles in vitiligo pathogenesis, some findings suggest their roles may be contradictory.

Objective: We aimed to assess IFN-γ, TNF-α and granzyme B levels in blood and skin of vitiligo patients using a meta-analysis approach. Additionally, we evaluated their association with disease activity.

Methods: A Meta-analysis was conducted using Review Manager 5.4 software. A total of 55 studies including 3,023 vitiligo patients and 2,534 controls were included in the study.

Results: Pooled results from our meta-analysis indicated significantly elevated IFN-γ protein and transcript levels in blood and skin of vitiligo patients (p < 0.05). TNF-α protein levels were also significantly increased in blood and skin of vitiligo patients (p < 0.05). IFN-γ and TNF-α levels were significantly higher in the lesional skin as compared to non-lesional skin (p < 0.05). Furthermore, elevated levels of IFN-γ and TNF-α were observed in patients with active vitiligo (p < 0.05). Additionally, our study suggested a significant increase in granzyme B levels in vitiligo patients (p < 0.05).

Conclusion: Overall, the meta-analysis suggests that IFN-γ, TNF-α and granzyme B play a crucial role in vitiligo pathogenesis and progression and may serve as potential therapeutic targets for managing the disease. The PROSPERO registration no. for meta-analysis is CRD42024620274.

Background: Over the last four decades, there has been a progressive increase in the number of publications and citations on research related to thyroid-associated ophthalmopathy (TAO) nonsurgical treatment across many countries/regions, institutions, and authors, with a special focus on biological immunotherapy.

Research design and methods: Examing 1600 publications collected from the Web of Science Core Collection database on TAO research from 1983 to 2023, our bibliometric analysis evaluated various bibliometric indicators, among which some important subtopics were identified and further discussed and reviewed.

Results: The study showed that novel insights into the pathogenesis of TAO and new immunological targets for nonsurgical treatments were the major research focus over the past 40 years. Especially, targeted biological immunotherapies were on the rise, promoting treatments efficacy and patients' quality of life.

Conclusions: Our study provided a thorough overview and visual presentation of the evolutionary landscape and emerging frontiers for nonsurgical treatment of TAO surrounding its immunological mechanism and therapeutic strategy. It also shed light on its global collaboration patterns, current trends and research hotspots, hopefully to facilitate collaborative initiatives and guiding future research.

Objective: This study investigated the correlation between serum Helios, CD226, TIGIT, and Foxp3 levels and tear film osmotic pressure in individuals with rheumatoid arthritis (RA) and dry eye disease.

Methods: This case-control study enrolled 100 RA patients with dry eye and 100 healthy controls from May 2021 to June 2022. mRNA expression of target genes was quantified using quantitative real-time PCR (qRT-PCR). Tear film osmolality was measured with a commercial osmometer. Statistical analyses included Pearson correlation and multivariate logistic regression.

Results: Compared with controls, RA patients exhibited significantly higher mRNA levels of Helios, CD226, TIGIT, and Foxp3 (p < 0.05), along with elevated mean tear osmolarity (312.5 ± 12.3 vs. 295.4 ± 10.8 milliosmoles per liter (mOsm/L), p < 0.05). Notably, 68% of RA patients exceeded the 308 mOsm/L diagnostic threshold versus 22% controls (p < 0.05). Helios (r = 0.62) and Foxp3 (r = 0.58) correlated positively with osmotic pressure, while TIGIT showed a negative correlation (r = -0.49, p < 0.05). Logistic regression revealed that elevated levels of Helios (OR = 2.1, 95% CI: 1.4-3.2), CD226 (OR = 1.8, 95% CI: 1.2-2.7), and Foxp3 (OR = 1.9, 95% CI: 1.3-2.8) were associated with increased dry eye risk (p < 0.05).

Conclusion: These immune markers demonstrate significant associations with tear film instability in RA, serving as potential biomarkers for ocular comorbidity monitoring.

Background: Colon adenocarcinoma (COAD) is a leading cause of cancer mortality, with Aquaporin 9 (AQP9) implicated in its progression. M2 macrophages in the tumor microenvironment (TME) promote cancer metastasis, but the role of AQP9 on M2 macrophages remains unelucidated.

Research design and methods: Using COAD cell lines, AQP9 expression was analyzed via RT-qPCR and Western blot (WB). Hypoxic conditions were simulated to assess HIF-1α and AQP9 interactions through ChIP and dual-luciferase assays. AQP9 knockdown effects on proliferation/migration were tested via colony formation and wound healing. M2 macrophage polarization and CD8+ T cell cytotoxicity were evaluated using flow cytometry, ELISA, and IHC in co-culture systems.

Results: AQP9 was upregulated in COAD and correlated with poor prognosis. After AQP9 in COAD cells was knocked down, the abilities of tumor cells to migrate and proliferate were dampened. Hypoxia upregulated HIF-1α, which transcriptionally activated AQP9. Knocking down AQP9 repressed the M2 polarization of macrophages, thereby reinforcing the cytotoxicity of CD8⁺ T cells. No adverse events were reported in vitro.

Conclusion: AQP9 promotes COAD progression by driving HIF-1α-mediated M2 polarization, impairing CD8+ T cell function. Key limitations include the lack of in vivo validation and clinical cohort analysis.

Introduction: Glucocorticoid (GC) remains the main stay of treatment for systemic lupus erythematosus (SLE) but is associated with a myriad of untoward effects. On the other hand, withdrawal of maintenance immunosuppression, including low-dose GCs, carries a risk of SLE flare.

Areas covered: The molecular mechanisms of GCs and their implications for dosing strategies in clinical practice are discussed. Evidence regarding withdrawal of maintenance immunosuppression in SLE is reviewed.

Expert opinions: The initial GC regimens for different manifestations of SLE are heterogeneous, with no major randomized controlled trials (RCTs) on their efficacy and toxicities available. RCTs on withdrawal of immunosuppressive drugs in quiescent SLE are inconsistent but appear to show an increase in disease flares, with risk factors being younger age, renal disease, cessation of hydroxychloroquine, shorter duration of remission, serological activity, and an abrupt tapering regime. The lowest effective doses of GC and immunosuppressive drugs should be adopted, and the decision to withdraw immunosuppression should be individualized. Newer strategies for GC sparing, including combination therapy of immunosuppressive and biological/targeted agents, and the use of methylprednisolone pulses for initial therapy of less serious manifestations of SLE, could ameliorate the toxicities of immunosuppression and help advance to the ultimate target of drug-free remission.

Introduction: Peripheral neuropathy (PN) may arise from various etiologies, including immune-mediated diseases. This study aimed to detect the prevalence and clinical determinants of PN in psoriatic arthritis (PsA) patients, with or without skin lesions, and to evaluate its correlation with disease activity.

Research design and methods: This cross-sectional study included 60 PsA patients and 60 apparently healthy controls. Neuropathic pain was evaluated using the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) score, while PN was assessed through the Michigan Neuropathy Screening Instrument (MNSI), in conjunction with electrophysiological assessment.

Results: The LANSS score demonstrated the capability to predict neuropathic pain in PsA patients with a sensitivity of 93.89% and specificity of 83.33%. Furthermore, the MNSI Questionnaire score revealed a sensitivity of 91.67% and specificity of 77.78% in predicting PN among PsA patients. Carpal tunnel syndrome represented the most prevalent neuropathy identified in 36% of PsA patients, followed by peripheral polyneuropathy in 6% and ulnar neuropathy in 4%.

Conclusions: Patients with PsA have higher prevalence of neuropathy, particularly carpal tunnel syndrome, which negatively impacts pain perception, functional capability, and quality of life, particularly in those with higher disease activity suggesting potential association between inflammation and neurological dysfunction.

Introduction: The variability in the efficacy of allergen-specific immunotherapy (AIT) for nasal symptom control can be attributed to individual differences, to explore the hypothesis of systematic variability in AR symptom alleviation with AIT and to determine whether this variability correlates with AR severity, route of administration, treatment duration, age, or study publication year.

Methods: We reviewed randomized controlled trials (RCTs) of AIT for dust mite (DM)-induced AR, extracting data on baseline mean, endpoint mean, standard deviation (SD), and participant numbers. A random-slope mixed-effects model (RSMM) was employed to evaluate the differences in variability between the AIT and control groups, as well as to identify potential influencing factors.

Results: There was no significant difference in response variability between the AIT and control groups. The response variability to AIT was not associated with AR severity, route of administration, age, or year of publication. The cohort that underwent 36 months of AIT exhibited a higher degree of response variability compared to the group treated for 6 months.

Conclusion: The present study did not identify systematic variability in individual response to AIT when measured by TNSS alone. More refined outcome measures and more associated factors are needed to explore personalized AIT in the future.

Introduction: The ubiquitin-proteasome system (UPS) is the major non-lysosomal mechanism for selective degradation of intracellular proteins that is essential for the regulation of cellular functions and survival. Modulation of the proteasomes and cereblon E3 ligase promotes degradation of polyubiquitin-tagged transcription factors and oncoproteins, leading to depletion of long-lived plasma cells, diminished autoantibody and interferon-α production, reduced T-cell polarization to the proinflammatory phenotypes and increased regulatory T-cell activity that are relevant to the therapy of systemic lupus erythematosus (SLE).

Areas covered: Selective immunoproteasome inhibitors and newer generation cereblon modulators have improved safety profiles compared to conventional compounds. This article summarizes the literature regarding the modulation of the UPS in murine and human SLE.

Expert opinion: Bortezomib and the selective immunoproteasome inhibitors, ONX-0914 and zetomipzomib, ameliorate renal disease in murine lupus models. While clinically effective in refractory SLE, bortezomib is limited by its toxicities. Zetomipzomib shows promising data in phase Ib/II studies of SLE and lupus nephritis. Thalidomide and lenalidomide are effective in refractory cutaneous lupus but again limited by their off-target effects. A phase II RCT of iberdomide shows favorable results in SLE, especially chronic and subacute cutaneous lesions. These molecules should be further explored in larger clinical trials of renal and cutaneous SLE.