Clinical & Translational Immunology最新文献

{"title":"A phase II study to evaluate the safety and efficacy of anlotinib combined with toripalimab for advanced biliary tract cancer","authors":"Mingzhen Zhou,&nbsp;Yuncheng Jin,&nbsp;Sihui Zhu,&nbsp;Chen Xu,&nbsp;Lin Li,&nbsp;Baorui Liu,&nbsp;Jie Shen","doi":"10.1002/cti2.1483","DOIUrl":"https://doi.org/10.1002/cti2.1483","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To assess the safety and efficacy of anlotinib (a multi-targeted tyrosine kinase inhibitor) combined with toripalimab (a PD-1 monoclonal antibody) in the treatment of unresectable biliary tract cancer (BTC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this prospective, single-arm, single-centre exploratory clinical study, patients with locally progressed or metastatic BTC were included. Patients were treated with anlotinib (12 mg, PO, QD, for 2 weeks and then stopped for a week, 21 days for a cycle) and toripalimab (240 mg, IV, Q3W). The primary endpoint of the study was the objective response rate (ORR), as defined in RECIST version 1.1 criteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this study, 15 BTC patients who met the criteria were enrolled. The ORR was 26.7%, the median progression-free survival (mPFS) was 8.6 months (95% CI: 2.1–15.2), the median overall survival (mOS) was 14.53 months (95% CI: 0.8–28.2) and the disease control rate (DCR) was 87.6%. A patient with hilar cholangiocarcinoma was successfully converted after three cycles of treatment and underwent surgical resection. Furthermore, patient gene sequencing revealed that STK11 was mutated more frequently in patients with poor outcomes. In addition, patients with a CD8/Foxp3 ratio &gt; 3 had a longer survival than those with a CD8/Foxp3 ratio ≤ 3 (<i>P</i> = 0.0397).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In patients with advanced BTC, the combination of anlotinib and toripalimab demonstrated remarkable anti-tumor potential, with increased objective response rates (ORR), longer overall survival (OS) and progression-free survival (PFS). Moreover, STK11 and CD8/Foxp3 may be as biomarkers that can predict the effectiveness of targeted therapy in combination with immunotherapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1483","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139435088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Graft CD8 T-cell-based risk system predicts survival in antithymocyte globulin-based myeloablative haploidentical peripheral blood stem cell transplantation","authors":"Panpan Zhu,&nbsp;Luxin Yang,&nbsp;Yibo Wu,&nbsp;Jimin Shi,&nbsp;Xiaoyu Lai,&nbsp;Lizhen Liu,&nbsp;Yishan Ye,&nbsp;Jian Yu,&nbsp;Yanmin Zhao,&nbsp;Xiaolin Yuan,&nbsp;Huarui Fu,&nbsp;Zhen Cai,&nbsp;He Huang,&nbsp;Yi Luo","doi":"10.1002/cti2.1484","DOIUrl":"https://doi.org/10.1002/cti2.1484","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study investigated the cellular composition of peripheral blood grafts for anti-thymocyte globulin (ATG)-based myeloablative haploidentical haematopoietic stem cell transplantation (haplo-HSCT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Clinical characteristics were retrospectively evaluated in a training cohort with ATG-based myeloablative haplo-HSCT between January 2016 and February 2020 and confirmed in a validation cohort between March 2020 and June 2021.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A higher dose of graft CD8⁺ T cells (≥ 0.85 × 10⁸ kg⁻¹) was significantly improved overall survival (OS; hazard ratio [HR], 1.750; <i>P</i> = 0.002) and disease-free survival (DFS; HR, 1.751; <i>P</i> &lt; 0.001) in the training cohort, according to multivariate Cox regression analysis. Higher doses of mononuclear cells (MNCs) demonstrated better OS (HR, 1.517; <i>P</i> = 0.038) and DFS (HR, 1.532; <i>P</i> = 0.027). Older patient age (&gt; 46 years), older donor age (≥ 50 years) and a higher refined disease risk index (rDRI) were also related to OS. A graft CD8⁺ T-cell risk system based on graft CD8⁺ T-cell dose, donor age and rDRI was constructed using a nomogram model after LASSO Cox regression analysis. It showed acceptable discrimination, with a C-index of 0.62 and 0.63, respectively. Graft CD8⁺ T-cell dose was negatively correlated with donor age (<i>P</i> &lt; 0.001) and positively correlated with a higher lymphocyte percentage in the peripheral blood before mobilisation (<i>P</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A higher CD8⁺ T-cell dose in peripheral blood-derived grafts improves patients' survival with ATG-based myeloablative haplo-HSCT. Younger donors with higher lymphocyte percentages improved patients' survival with an intermediate rDRI risk.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1484","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139435089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular models in autoinflammatory disease research","authors":"Başak Şen,&nbsp;Banu Balcı-Peynircioğlu","doi":"10.1002/cti2.1481","DOIUrl":"10.1002/cti2.1481","url":null,"abstract":"<p>Systemic autoinflammatory diseases are a heterogeneous group of rare genetic disorders caused by dysregulation of the innate immune system. Understanding the complex mechanisms underlying these conditions is critical for developing effective treatments. Cellular models are essential for identifying new conditions and studying their pathogenesis. Traditionally, these studies have used primary cells and cell lines of disease-relevant cell types, although newer induced pluripotent stem cell (iPSC)-based models might have unique advantages. In this review, we discuss the three cellular models used in autoinflammatory disease research, their strengths and weaknesses, and their applications to inform future research in the field.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10784111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139424146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD14 down-modulation as a real-time biomarker in Kawasaki disease","authors":"Yutaro Inada,&nbsp;Motoshi Sonoda,&nbsp;Yumi Mizuno,&nbsp;Kenichiro Yamamura,&nbsp;Yoshitomo Motomura,&nbsp;Aoba Takuma,&nbsp;Kenji Murata,&nbsp;Kenji Furuno,&nbsp;Junichiro Tezuka,&nbsp;Yasunari Sakai,&nbsp;Shouichi Ohga,&nbsp;Junji Kishimoto,&nbsp;Koki Hosaka,&nbsp;Satomi Sakata,&nbsp;Toshiro Hara","doi":"10.1002/cti2.1482","DOIUrl":"10.1002/cti2.1482","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The objectives of this study were to investigate the pathophysiology of Kawasaki disease (KD) from immunological and oxidative stress perspectives, and to identify real-time biomarkers linked to innate immunity and oxidative stress in KD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We prospectively enrolled 85 patients with KD and 135 patients with diverse conditions including immune, infectious and non-infectious diseases for this investigation. Flow cytometry was used to analyse the surface expression of CD14, CD38 and CD62L on monocytes, along with a quantitative assessment of CD14 down-modulation. Additionally, oxidative stress levels were evaluated using derivatives of reactive oxygen metabolites (d-ROMs) and antioxidant capacity measured by a free radical elective evaluator system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>During the acute phase of KD, we observed a prominent CD14 down-modulation on monocytes, reflecting the indirect detection of circulating innate immune molecular patterns. Moreover, patients with KD showed a significantly higher CD14 down-modulation compared with infectious and non-infectious disease controls. Notably, the surface expression of CD14 on monocytes was restored concurrently with responses to intravenous immunoglobulin and infliximab treatment in KD. Furthermore, d-ROM levels in patients with KD were significantly elevated compared with patients with infectious and non-infectious diseases. Following intravenous immunoglobulin treatment, oxidative stress levels decreased in patients with KD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Monitoring CD14 down-modulation on monocytes in real-time is a valuable strategy for assessing treatment response, distinguishing KD relapse from concomitant infections and selecting second-line therapy after IVIG treatment in KD patients. The interplay between inflammation and oxidative stress likely plays a crucial role in the development of KD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1482","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139069630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammatory cytokines as mediators of retinal endothelial barrier dysfunction in non-infectious uveitis","authors":"Lisia Barros Ferreira,&nbsp;Keryn A Williams,&nbsp;Giles Best,&nbsp;Cameron D Haydinger,&nbsp;Justine R Smith","doi":"10.1002/cti2.1479","DOIUrl":"https://doi.org/10.1002/cti2.1479","url":null,"abstract":"<p>Characterised by intraocular inflammation, non-infectious uveitis includes a large group of autoimmune and autoinflammatory diseases that either involve the eye alone or have both ocular and systemic manifestations. When non-infectious uveitis involves the posterior segment of the eye, specifically the retina, there is substantial risk of vision loss, often linked to breakdown of the inner blood-retinal barrier. This barrier is formed by non-fenestrated retinal vascular endothelial cells, reinforced by supporting cells that include pericytes, Müller cells and astrocytes. Across the published literature, a group of inflammatory cytokines stand out as prominent mediators of intraocular inflammation, with effects on the retinal endothelium that may contribute to breakdown of the inner blood-retinal barrier, namely tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, IL-17 and chemokine C-C motif ligand (CCL)2. This article reviews the function of each cytokine and discusses the evidence for their involvement in retinal endothelial barrier dysfunction in non-infectious uveitis, including basic laboratory investigations, studies of ocular fluids collected from patients with non-infectious uveitis, and results of clinical treatment trials. The review also outlines gaps in knowledge in this area. Understanding the disease processes at a molecular level can suggest treatment alternatives that are directed against appropriate biological targets to protect the posterior segment of eye and preserve vision in non-infectious uveitis.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 12","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1479","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138571055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced and complementary benefits of a nalfurafine and fingolimod combination to treat immune-driven demyelination","authors":"Katharina Robichon,&nbsp;Rabia Bibi,&nbsp;Mackenzie Kiernan,&nbsp;Lisa Denny,&nbsp;Thomas E Prisinzano,&nbsp;Bronwyn M Kivell,&nbsp;Anne Camille La Flamme","doi":"10.1002/cti2.1480","DOIUrl":"https://doi.org/10.1002/cti2.1480","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Multiple sclerosis (MS) is a neurodegenerative disease characterised by inflammation and damage to myelin sheaths. While all current disease-modifying treatments (DMTs) are very effective at reducing relapses, they do not slow the progression of the disease, and there is little evidence that these treatments are able to repair or remyelinate damaged axons. Recent evidence suggests that activating kappa opioid receptors (KORs) has a beneficial effect on the progression of MS, and this study investigates the effects of KOR agonists treatment in combination with two current DMTs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the well-established murine model for immune-driven demyelination of MS, experimental autoimmune encephalomyelitis, the effect of KOR agonists in combination with DMTs fingolimod or dimethyl fumarate on disease progression, immune cell infiltration and activation as well as myelination were analysed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fingolimod in combination with the KOR agonist, nalfurafine, significantly increased each individual beneficial effect as measured by increased recovery of mice and reduced relapses. These beneficial effects correlated with a reduction in immune cell infiltration into the CNS as well as peripheral immune cell alterations including a reduction in autoreactive CD4⁺ T-cell cytokine production as well as increased myelination in the spinal cords of co-treated animals. In contrast, while the use of dimethyl fumarate in combination with nalfurafine did not adversely affect the benefits of nalfurafine, the combination did not significantly enhance those benefits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study indicates that KOR agonists can be used in combination with fingolimod and dimethyl fumarate with the nalfurafine–fingolimod combination providing enhanced benefits.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 12","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1480","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138571043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated BMI reduces the humoral response to SARS-CoV-2 infection","authors":"Marcus ZW Tong,&nbsp;Julian DJ Sng,&nbsp;Meagan Carney,&nbsp;Lucy Cooper,&nbsp;Samuel Brown,&nbsp;Katie E Lineburg,&nbsp;Keng Yih Chew,&nbsp;Neve Collins,&nbsp;Kirsten Ignacio,&nbsp;Megan Airey,&nbsp;Lucy Burr,&nbsp;Briony A Joyce,&nbsp;Dhilshan Jayasinghe,&nbsp;Christopher LD McMillan,&nbsp;David A Muller,&nbsp;Anurag Adhikari,&nbsp;Linda A Gallo,&nbsp;Emily S Dorey,&nbsp;Helen L Barrett,&nbsp;Stephanie Gras,&nbsp;Corey Smith,&nbsp;Kim Good-Jacobson,&nbsp;Kirsty R Short","doi":"10.1002/cti2.1476","DOIUrl":"https://doi.org/10.1002/cti2.1476","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Class III obesity (body mass index [BMI] ≥ 40 kg m⁻²) significantly impairs the immune response to SARS-CoV-2 vaccination. However, the effect of an elevated BMI (≥ 25 kg m⁻²) on humoral immunity to SARS-CoV-2 infection and COVID-19 vaccination remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We collected blood samples from people who recovered from SARS-CoV-2 infection approximately 3 and 13 months of post-infection (noting that these individuals were not exposed to SARS-CoV-2 or vaccinated in the interim). We also collected blood samples from people approximately 5 months of post-second dose COVID-19 vaccination (the majority of whom did not have a prior SARS-CoV-2 infection). We measured their humoral responses to SARS-CoV-2, grouping individuals based on a BMI greater or less than 25 kg m⁻².</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Here, we show that an increased BMI (≥ 25 kg m⁻²), when accounting for age and sex differences, is associated with reduced antibody responses after SARS-CoV-2 infection. At 3 months of post-infection, an elevated BMI was associated with reduced antibody titres. At 13 months of post-infection, an elevated BMI was associated with reduced antibody avidity and a reduced percentage of spike-positive B cells. In contrast, no significant association was noted between a BMI ≥ 25 kg m⁻² and humoral immunity to SARS-CoV-2 at 5 months of post-secondary vaccination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Taken together, these data showed that elevated BMI is associated with an impaired humoral immune response to SARS-CoV-2 infection. The impairment of infection-induced immunity in individuals with a BMI ≥ 25 kg m⁻² suggests an added impetus for vaccination rather than relying on infection-induced immunity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 12","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1476","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138480933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in immune cell populations following KappaMab, lenalidomide and low-dose dexamethasone treatment in multiple myeloma","authors":"Samuel E Norton,&nbsp;Tiffany Khong,&nbsp;Malarmathy Ramachandran,&nbsp;Andrew J Highton,&nbsp;Kirsten A Ward-Hartstonge,&nbsp;Jake Shortt,&nbsp;Andrew Spencer,&nbsp;Roslyn A Kemp","doi":"10.1002/cti2.1478","DOIUrl":"10.1002/cti2.1478","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Lenalidomide (LEN) is used to treat multiple myeloma (MM) and shows <i>in vitro</i> synergy with KappaMab (KM), a chimeric antibody specific for Kappa Myeloma antigen, an antigen exclusively expressed on the surface of kappa-restricted MM cells. Lenalidomide, dexamethasone (DEX) and KM control MM <i>via</i> multiple immunomodulatory mechanisms; however, there are several additional effects of the drug combination on immune cells. Lenalidomide can increase T cell and NKT cell cytotoxicity and dendritic cell (DC) activation <i>in vitro</i>. We investigated the immune cell populations in bone marrow of patients treated with KM, LEN and low-dose DEX in kappa-restricted relapsed/refractory MM <i>ex vivo</i> and assessed association of those changes with patient outcome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cohort (<i>n</i> = 40) of patients with kappa-restricted relapsed/refractory MM, treated with KM, LEN and low-dose DEX, was analysed using a mass cytometry panel that allowed identification of immune cell subsets. Clustering analyses were used to determine significant changes in immune cell populations at time periods after treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found changes in five DC and 17 T-cell populations throughout treatment. We showed an increase in activated conventional DC populations, a decrease in immature/precursor DC populations, a decrease in activated CD4 T cells and an increase in effector-memory CD4 T cells and effector CD8 T cells, indicating an activated immune response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These data characterise the effects of LEN, DEX, and KM treatment on non-target immune cells in MM. Treatment may support destruction of MM cells by both direct action and indirect mechanisms <i>via</i> immune cells.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 12","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10688504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138456636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The spectrum of B cells in the pathogenesis, diagnosis and therapeutic applications of immunoglobulin G4-related disease","authors":"Qiyuan Hao,&nbsp;Meng Sun,&nbsp;Yanying Liu","doi":"10.1002/cti2.1477","DOIUrl":"https://doi.org/10.1002/cti2.1477","url":null,"abstract":"<p>Immunoglobulin G4 (IgG4)-related disease is a chronic fibroinflammatory disease mediated by immune disorders. Given the challenging clinical diagnosis and treatment, knowledge of the pathogenesis of IgG4-related disease is important. The typical elevation of serum IgG4 concentrations and infiltration of IgG4-positive plasma cells in the involved tissues indicate the involvement of B lymphocytes in the pathogenesis of IgG4-related disease. Mass production of autoantibodies reflects abnormal activation of B cells, which causes tissue damage. Circulating plasmablasts are recently discovered markers that correlate with serum IgG4 concentration, the extent of organ involvement and disease activity. B-cell depletion therapy is an emerging curative strategy that can significantly alleviate clinical manifestations and achieve remission in patients with IgG4-related disease. These findings highlight the potential role of B cells in IgG4-related disease. In this review, we discuss the pathogenic impact of B lymphocytes on IgG4-related disease and describe novel therapies targeting B cells.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 12","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1477","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138454728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating cytokine and chemokine patterns associated with cytomegalovirus reactivation after stem cell transplantation","authors":"Lauren Stern,&nbsp;Helen M McGuire,&nbsp;Selmir Avdic,&nbsp;Emily Blyth,&nbsp;David Gottlieb,&nbsp;Ellis Patrick,&nbsp;Allison Abendroth,&nbsp;Barry Slobedman","doi":"10.1002/cti2.1473","DOIUrl":"https://doi.org/10.1002/cti2.1473","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Human cytomegalovirus (HCMV) reactivation is the leading viral complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Understanding of circulating cytokine/chemokine patterns which accompany HCMV reactivation and correlate with HCMV DNAemia magnitude is limited. We aimed to characterise plasma cytokine/chemokine profiles in 36 allo-HSCT patients (21 with HCMV reactivation and 15 without HCMV reactivation) at four time-points in the first 100-day post-transplant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The concentrations of 31 cytokines/chemokines in plasma samples were analysed using a multiplex bead-based immunoassay. Cytokine/chemokine concentrations were compared in patients with high-level HCMV DNAemia, low-level HCMV DNAemia or no HCMV reactivation, and correlated with immune cell frequencies measured using mass cytometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Increased plasma levels of T helper 1-type cytokines/chemokines (TNF, IL-18, IP-10, MIG) were detected in patients with HCMV reactivation at the peak of HCMV DNAemia, relative to non-reactivators. Stem cell factor (SCF) levels were significantly higher before the detection of HCMV reactivation in patients who went on to develop high-level HCMV DNAemia (810–52 740 copies/mL) <i>vs.</i> low-level HCMV DNAemia (&lt; 250 copies/mL). High-level HCMV reactivators, but not low-level reactivators, developed an elevated inflammatory cytokine/chemokine profile (MIP-1α, MIP-1β, TNF, LT-α, IL-13, IL-9, SCF, HGF) at the peak of reactivation. Plasma cytokine concentrations displayed unique correlations with circulating immune cell frequencies in patients with HCMV reactivation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study identifies distinct circulating cytokine/chemokine signatures associated with the magnitude of HCMV DNAemia and the progression of HCMV reactivation after allo-HSCT, providing important insight into immune recovery patterns associated with HCMV reactivation and viral control.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 12","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1473","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138454727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}