Clinical & Translational Immunology最新文献

{"title":"γδ T cell characterisation in the long term after haematopoietic stem cell transplantation and its impact on CMV control and cGVHD severity","authors":"Faisal Alagrafi,&nbsp;Arwen Stikvoort,&nbsp;Ahmed Gaballa,&nbsp;Martin Solders,&nbsp;Olle Ringden,&nbsp;Thomas Poiret,&nbsp;Lucas CM Arruda,&nbsp;Michael Uhlin","doi":"10.1002/cti2.70027","DOIUrl":"https://doi.org/10.1002/cti2.70027","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The clinical outcome after allogeneic haematopoietic stem cell transplantation (aHCT) relies greatly on the efficient recovery of T cells. Several studies have investigated the short-term γδ T cell reconstitution and their role in clinical outcomes following haematopoietic stem cell transplantation. Nevertheless, their long-term characteristics and impact have remained largely unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed γδ T cells from 20 recipient/donor pairs at phenotypic, clonotypic and functional levels to assess their reconstitution ≥ 8 years (median 18 years) post-transplantation using high-parameter flow cytometry and next-generation sequencing of the TCR γ-chain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>γδ T cells displayed comparable phenotypic characteristics between recipients and matching donors. The Vδ2⁺ subset showed a more activated phenotype and cytokine production, while the Vδ1⁺ and non-Vδ2 T cells maintained long-term CMV control. TCR γ-chain composition in long-term survivors was largely restored, with no significant differences in gene segment usage or diversity. A small cohort of recipients with severe chronic graft-versus-host disease (GVHD) showed overrepresented donor-derived private clonotypes. Furthermore, we also found elevated HLA-DR⁺Vδ1⁺ T cells in recipients with severe chronic GVHD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Overall, γδ T cells reconstitute with a normalised repertoire, high functional capacity and sustained CMV control ability. An increased proportion of activated Vδ1⁺ T cells correlates with chronic GVHD severity, indicating a potential therapeutic target.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 3","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565227","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":"Distinct MAIT cell phenotypes associated with sepsis clinical outcome in emergency department patients","authors":"Johanna Emgård,&nbsp;Iva Filipovic,&nbsp;Christian Unge,&nbsp;Laura M Palma Medina,&nbsp;Åsa Parke,&nbsp;Helena Bergsten,&nbsp;Kirsten Moll,&nbsp;Majda Dzidic,&nbsp;Helena Alpkvist,&nbsp;Hong Fang,&nbsp;Volkan Özenci,&nbsp;Niklas K Björkström,&nbsp;Mattias Svensson,&nbsp;Johan K Sandberg,&nbsp;Kristoffer Strålin,&nbsp;Anna Norrby-Teglund","doi":"10.1002/cti2.70028","DOIUrl":"https://doi.org/10.1002/cti2.70028","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Rapid diagnosis and intervention are critical for sepsis patient outcomes. However, diagnosis is challenging because of a heterogenic patient group as well as sometimes vague symptoms when the patient presents at the emergency department. Mucosal-associated invariant T (MAIT) cells are rapid responders to infection, but their role and characteristics in the early course of sepsis remain unknown. Here, we evaluate the early MAIT cell characteristics in the blood of patients triggering a clinical sepsis alert system at the emergency department.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Peripheral blood mononuclear cells were isolated from freshly drawn blood and immediately stained. MAIT cell phenotyping analyses were conducted using multiparameter flow cytometry. All analyses were completed prior to the stratification of patients into sepsis or non-sepsis groups. Soluble factors in plasma were measured using a multiplex assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Unsupervised high-dimensional phenotyping identified distinct MAIT cell activation profiles in sepsis and non-sepsis groups. Among sepsis patients, hierarchical clustering of MAIT cell phenotypes separated clinical endotypes into three groups with different infection focus, severity and aetiology. A prominent characteristic of sepsis severity was high expression of CD69 on MAIT cells, which was associated with organ dysfunction, lymphopenia and poor outcome. Plasma levels of IL-12, IL-15, TNF, IFNγ and CXCL10 correlated with the magnitude of MAIT cell activation in sepsis patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These clinical endotype-specific MAIT cell phenotypes presenting already in the emergency department are of interest for early patient identification and prognostication in sepsis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 3","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554605","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":"Decreased levels and function of dendritic cells in blood and airways predict COVID-19 severity","authors":"Björn Österberg,&nbsp;Sara Falck-Jones,&nbsp;Sindhu Vangeti,&nbsp;Eric Åhlberg,&nbsp;Meng Yu,&nbsp;Diana Granja,&nbsp;Marijn E Snik,&nbsp;Ryan Falck-Jones,&nbsp;Guilherme WF Barros,&nbsp;Afandi Charles,&nbsp;Rico Lepzien,&nbsp;Niclas Johansson,&nbsp;Tyson H Holmes,&nbsp;Holden Maecker,&nbsp;Paulo Czarnewski,&nbsp;Max Bell,&nbsp;Anna Färnert,&nbsp;Anna Smed-Sörensen","doi":"10.1002/cti2.70026","DOIUrl":"https://doi.org/10.1002/cti2.70026","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Monocytes and dendritic cells (DCs) are essential players in the immune response to infections, involved in shaping innate and adaptive immunity. However, a complete understanding of their specific roles in respiratory infections, including SARS-CoV-2, remains elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To investigate the dynamics of monocytes and DCs in blood as well as the upper and lower airways, we sampled 147 patients with varying degree of COVID-19 severity longitudinally during the spring of 2020.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Using flow cytometry, proteomics and <i>in vitro</i> TLR stimulation, we found differences in the distribution and function of monocytes and DCs in patients compared with controls, and importantly, reduced levels of DCs in both blood and airways. In fact, lower frequencies of cDC2s (Lin⁻ HLA-DR⁺ CD1c⁺) early after symptom onset predicted subsequent severe disease, and depletion of DC subsets lasted longer in patients with more severe disease. In contrast, severe COVID-19 was associated with increased frequencies of activated monocytes in the lower, but not the upper, airways. Proteomic analysis showed that monocyte and DC-related cytokines in plasma and airways associated with disease severity. During convalescence, cell frequencies and responses to TLR ligands normalised in blood, except for persistently low plasmacytoid DCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study reveals a distinct pattern of recruitment of monocytes but not DCs to the airways during severe COVID-19. Instead, decreased levels of DCs in both blood and airways were found, possibly contributing to more severe COVID-19. The connection between low blood DCs early in disease course and more severe outcomes provides insight into COVID-19 immunopathology, with possible therapeutic implications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 3","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530404","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":"Organ-on-chip for advancing CAR therapy","authors":"Lightson Ngashangva,&nbsp;Sunil Martin","doi":"10.1002/cti2.70024","DOIUrl":"https://doi.org/10.1002/cti2.70024","url":null,"abstract":"<p>Despite great strides of progress, at least 60% of the responding patients relapse to CAR therapy across the blood malignancies. Off-tumor toxicity apart from functional deficits, cytopenia and infection are the major unfavourable effect of CAR therapy. Models, which faithfully recapitulate the physiology and complexities of immunocompetent tumor microenvironment (TME), paused challenges in capturing potential off-tumor effects of CAR therapy. Importantly, a landmark change in the legislation allows US Food and Drug Administration and New Drugs and Clinical Trial Rules in India encourages researchers to replace animal testing with cell culture approaches relevant to human system. Organ-on-chip (OOC) based on microfluidics technology can potentially emulate multiple biochemical and biophysical intricacies of blood and lymph flow at microscale. Nonetheless, how the evolving microfluidics technology can be enabling to real-time testing of cell and gene is yet to be realised.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 2","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489966","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":"Effect of Bacille Calmette–Guérin vaccination on immune responses to SARS-CoV-2 and COVID-19 vaccination","authors":"Nicole L Messina,&nbsp;Susie Germano,&nbsp;Amy W Chung,&nbsp;Carolien E van de Sandt,&nbsp;Natalie E Stevens,&nbsp;Lilith F Allen,&nbsp;Rhian Bonnici,&nbsp;Julio Croda,&nbsp;Claudio Counoupas,&nbsp;Branka Grubor-Bauk,&nbsp;Ebene R Haycroft,&nbsp;Katherine Kedzierska,&nbsp;Ellie McDonald,&nbsp;Rebecca McElroy,&nbsp;Mihai G Netea,&nbsp;Boris Novakovic,&nbsp;Kirsten P Perrett,&nbsp;Laure F Pittet,&nbsp;Ruth A Purcell,&nbsp;Kanta Subbarao,&nbsp;James A Triccas,&nbsp;David J Lynn,&nbsp;Nigel Curtis,&nbsp;the BRACE Trial Consortium Group","doi":"10.1002/cti2.70023","DOIUrl":"10.1002/cti2.70023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Bacille Calmette–Guérin (BCG) vaccination has off-target effects on disease risk for unrelated infections and immune responses to vaccines. This study aimed to determine the immunomodulatory effects of BCG vaccination on immune responses to vaccines against SARS-CoV-2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Blood samples, from a subset of 275 SARS-CoV-2-naïve healthcare workers randomised to BCG vaccination (BCG group) or no BCG vaccination (Control group) in the BRACE trial, were collected before and 28 days after the primary course (two doses) of ChAdOx1-S (Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech) vaccination. SARS-CoV-2-specific antibodies were measured using ELISA and multiplex bead array, whole blood cytokine responses to γ-irradiated SARS-CoV-2 (iSARS) stimulation were measured by multiplex bead array, and SARS-CoV-2-specific T-cell responses were measured by activation-induced marker and intracellular cytokine staining assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After randomisation (mean 11 months) but prior to COVID-19 vaccination, the BCG group had lower cytokine responses to iSARS stimulation than the Control group. After two doses of ChAdOx1-S, differences in iSARS-induced cytokine responses between the BCG group and Control group were found for three cytokines (CTACK, TRAIL and VEGF). No differences were found between the groups after BNT162b2 vaccination. There were also no differences between the BCG and Control groups in COVID-19 vaccine-induced antigen-specific antibody responses, T-cell activation or T-cell cytokine production.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>BCG vaccination induced a broad and persistent reduction in <i>ex vivo</i> cytokine responses to SARS-CoV-2. Following COVID-19 vaccination, this effect was abrogated, and BCG vaccination did not influence adaptive immune responses to COVID-19 vaccine antigens.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051099","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":"Autoantibodies in hospitalised patients with COVID-19","authors":"Eleni Tiniakou,&nbsp;Livia Casciola-Rosen,&nbsp;Mekha A Thomas,&nbsp;Yuka Manabe,&nbsp;Annukka AR Antar,&nbsp;Mahendra Damarla,&nbsp;Paul M Hassoun,&nbsp;Li Gao,&nbsp;Zitong Wang,&nbsp;Scott Zeger,&nbsp;Antony Rosen","doi":"10.1002/cti2.70019","DOIUrl":"10.1002/cti2.70019","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>CD209L and its homologous protein CD209 act as alternative entry receptors for the SARS-CoV-2 virus and are highly expressed in the virally targeted tissues. We tested for the presence and clinical features of autoantibodies targeting these receptors and compared these with autoantibodies known to be associated with COVID-19.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using banked samples (<i>n</i> = 118) from Johns Hopkins patients hospitalised with COVID-19, we defined autoantibodies against CD209 and CD209L by enzyme-linked immunosorbent assay (ELISA). Clinical associations of these antibodies were compared with those of patients with anti-interferon (IFN) and anti-angiotensin-converting enzyme-2 (ACE2) autoantibodies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Amongst patients hospitalised with COVID-19, 19.5% (23/118) had IgM autoantibodies against CD209L and were more likely to have coronary artery disease (44% vs 19%, <i>P</i> = 0.03). Antibodies against CD209 were present in 5.9% (7/118); interestingly, all 7 were male (<i>P</i> = 0.02). In our study, the presence of either antibody was positively associated with disease severity [OR 95% confidence interval (95% CI): 1.80 (0.69–5.03)], but the association did not reach statistical significance. In contrast, 10/118 (8.5%) had IgG autoantibodies against IFNα, and 21 (17.8%) had IgM antibodies against ACE2. These patients had significantly worse prognosis (intubation or death) and prolonged hospital stays. However, when adjusting for patient characteristics on admission, only the presence of anti-ACE2 IgM remained significant [pooled common OR (95% CI), 4.14 (1.37, 12.54)].</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We describe IgM autoantibodies against CD209 and CD209L amongst patients hospitalised with COVID-19. These were not associated with disease severity. Conversely, patients with either anti-ACE2 IgM or anti-IFNα IgG antibodies had worse outcomes. Due to the small size of the study cohort, conclusions drawn should be considered cautiously.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 12","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902525","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":"A preclinical study of allogeneic CD19 chimeric antigen receptor double-negative T cells as an off-the-shelf immunotherapy drug against B-cell malignancies","authors":"Dan Wang,&nbsp;Liuyang Wang,&nbsp;Shuai Liu,&nbsp;Jianjun Tong,&nbsp;Honglin Zhu,&nbsp;Man Xu,&nbsp;Xiancai Li,&nbsp;Zhiqiang Xiang,&nbsp;Qinghua Sun,&nbsp;Hengcai Wang,&nbsp;Yuli Wang,&nbsp;Shuyang Wang,&nbsp;Liming Yang","doi":"10.1002/cti2.70022","DOIUrl":"10.1002/cti2.70022","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To evaluate the manufacturability, efficacy and safety of allogeneic CD19 chimeric antigen receptor double-negative T cells (CD19-CAR-DNTs) as an off-the-shelf therapeutic cell product.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A membrane proteome array was used to assess the off-target binding of CD19-CAR. DNTs derived from healthy donors were transduced with lentiviral vectors encoding the CD19-CAR. The manufacture of the CD19-CAR-DNTs was under GMP conditions, and their surface molecule expression patterns were characterised using flow cytometry. We investigated the off-the-shelf potential of CD19-CAR-DNTs by evaluating the cryopreserved CD19-CAR-DNTs in terms of cell viability as well as their cytotoxicity against various CD19⁺ target cell lines and primary patient blasts <i>in vitro.</i> We evaluated the persistence and safety of the cryopreserved CD19-CAR-DNTs in xenograft models <i>in vivo</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>GMP-grade CD19-CAR-DNTs were manufactured and cryopreserved for use in advance. The cryopreserved CD19-CAR-DNTs maintain their viability and antitumor activity against various CD19⁺ target cell lines and primary patient blasts. These cells significantly prolonged the survival in Raji-Luc-xenografted NOG mice. Multiple infusions of the cells can further augment their efficacy. Remarkably, following a single infusion in mice, CD19-CAR-DNTs rapidly got distributed among well-perfused organs initially, and progressively spread to most tissues, peaking at Day 43. In toxicity studies, CD19-CAR-DNTs significantly reduced tumor burden and ameliorated tissue damage in tumor-bearing NOG mice. Critically, no immunotoxicity or graft versus host disease was observed in non-tumor-bearing NOG mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The allogeneic CD19-CAR-DNTs fulfil the requirements of an off-the-shelf therapeutic cell product, offering a promising new approach to the treatment of haematological malignancies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 12","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884898","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":"Improving diagnosis in patients with obstetric antiphospholipid syndrome through the evaluation of non-criteria antibodies","authors":"Daniel Álvarez,&nbsp;Hephzibah E Winter,&nbsp;Carlos J Velasquez Franco,&nbsp;Aleida Susana Castellanos Gutierrez,&nbsp;Núria Baños,&nbsp;Udo R Markert,&nbsp;Ángela P Cadavid,&nbsp;Diana M Morales-Prieto","doi":"10.1002/cti2.70021","DOIUrl":"10.1002/cti2.70021","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Antiphospholipid syndrome (APS) is an autoimmune disease driven by antiphospholipid antibodies (aPL). Currently, APS diagnosis requires a combination of clinical manifestations (thrombosis and/or obstetric morbidity) and the persistent presence of at least one criteria aPL: anti-cardiolipin antibodies (aCL), anti-β2-glycoprotein I antibodies (aβ2GPI) or lupus anticoagulant (LA). Patients with suggestive obstetric symptoms but lacking criteria aPL face diagnostic challenges. Non-criteria aPL screening may enhance discrimination. This study proposes a classification incorporating both criteria and non-criteria antibodies to improve obstetric APS diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Blood samples from non-pregnant women (<i>n</i> = 68) with a history of vascular, obstetric, or vascular and obstetric manifestations were analysed. Among them, 30 had previous diagnosis of APS. Healthy women with proven gestational success were included as controls (<i>n</i> = 16). Criteria and non-criteria (anti-phosphatidylglycerol, anti-phosphatidylethanolamine, anti-phosphatidylinositol, anti-phosphatidylserine and anti-phosphatidic acid) IgG aPL were evaluated by ELISA and coagulation tests. Based on the resulting aPL profile, patients were reclassified. Responsiveness to treatment was obtained from medical records.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Criteria aPL levels marginally differentiated women previously managed as obstetric APS from unexplained/other causes of obstetric morbidity. Including non-criteria aPL improved separation. The proposed classification identified an obstetric APS group that exhibits non-criteria aPL and aβ2GPI titres below the cut-off but higher than healthy women (7.88 vs. 2.47 SGU, <i>P</i> = 0.006). Compared to cases of other causes of obstetric morbidity, these patients retrospectively responded better to aspirin and/or heparin treatment (71.43% vs. 11.11%, <i>P</i> = 0.035).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Assessing non-criteria antibodies may identify isolated obstetric APS cases benefiting from established therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 12","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826958","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":"From the bench to the clinic: basophils and type 2 epithelial cytokines of thymic stromal lymphopoietin and IL-33","authors":"Kazushige Obata-Ninomiya,&nbsp;Tharmalingam Jayaraman,&nbsp;Steven F Ziegler","doi":"10.1002/cti2.70020","DOIUrl":"10.1002/cti2.70020","url":null,"abstract":"<p>Type 2 epithelial cytokines, including thymic stromal lymphopoietin and IL-33, play central roles in modulation of type 2 immune cells, such as basophils. Basophils are a small subset of granulocytes within the leukocyte population that predominantly exist in the blood. They have non-redundant roles in allergic inflammation in peripheral tissues such as the lung, skin and gut, where they increase and accumulate at inflammatory lesions and exclusively produce large amounts of IL-4, a type 2 cytokine. These inflammatory reactions are known to be, to some extent, phenocopies of infectious diseases of ticks and helminths. Recently, biologics related to both type 2 epithelial cytokines and basophils have been approved by the US Food and Drug Administration for treatment of allergic diseases. We summarised the roles of Type 2 epithelial cytokines and basophils in basic science to translational medicine, including recent findings.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 12","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798778","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":"Squamous cell carcinoma is associated with reduced IL34 expression, alterations in the Langerhans cell antigen-processing-presentation machinery and poor patient survival","authors":"Thi Viet Trinh Dang,&nbsp;Kevin R Gillinder,&nbsp;Quan Nguyen,&nbsp;Onkar Mulay,&nbsp;Tuan Vo,&nbsp;Ahmed M Mehdi,&nbsp;Chenhao Zhou,&nbsp;Andrew J Brooks,&nbsp;Graham R Leggatt,&nbsp;David A Hume,&nbsp;Ian H Frazer,&nbsp;Janin Chandra","doi":"10.1002/cti2.70018","DOIUrl":"https://doi.org/10.1002/cti2.70018","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Langerhans cells (LCs) are epithelial antigen-presenting cells (APC) contributing to immune surveillance. LCs depend on interleukin 34 (IL34) production by epithelial cells. This study aimed to uncover mechanisms of alteration of IL34 and LC function in squamous cell carcinoma (SCC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cancer cohort data were used to identify associations between SCC and IL34. ATAC-seq of keratinocytes (KCs) and LCs from a murine model of epithelial hyperplasia, driven by HPV16 E7 oncoprotein (K14E7), was analysed. Transcriptomic data were used to validate findings. RNAscope, RT-qPCR, ELISA and confocal imaging was used to analyse IL34 expression and LCs in a spatial context.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>IL34</i> mRNA is downregulated in human SCCs of the head and neck, the cervix, the lung and the oesophagus, and low <i>IL34</i> expression is associated with poor survival. We demonstrate that KCs of K14E7 mice have reduced <i>Il34</i> gene accessibility, mRNA and protein, as well as broad changes in promotor accessibility associated with cell adhesion and immune responses. Chromatin accessibility was substantially changed in LCs, including increased accessibility of the <i>Csf1r</i> gene, and changes in promotors associated with cytoskeleton arrangement and antigen processing and presentation. We discovered altered spatial LC dendrite organisation in hyperproliferative epithelium.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Squamous cell carcinoma of the cervix, head and neck, oesophagus and lung demonstrate downregulation of IL34, which is associated with poor survival, and with alterations in LC spatial organisation and function. These findings suggest that reduced IL34 expression in SCC may contribute to impaired local immunity through LC dysregulation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 12","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749098","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}