Pub Date : 2025-11-07DOI: 10.1016/j.clim.2025.110638
Qian Ye , Jin Rao , Li Zhang , Muxia Yan , Huishan Chen , Yanping Yi , Hua Jiang , Xiaoliang Deng , Yiqian Wang
Pediatric acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, yet reliable serum biomarkers for prognosis and relapse prediction remain limited. We profiled serum cytokines in 60 pediatric ALL patients and 19 healthy controls using the Aimplex Cytokine Assay, and evaluated predictive performance via receiver operating characteristic (ROC) analysis and least absolute shrinkage and selection operator (LASSO) regression. ALL patients exhibited significantly elevated levels of IFN-γ, IL-2, IL-4, IL-10, IL-17A, and TNF-α compared with controls. Among these, IL-17A and IL-10 showed the strongest associations with disease severity and relapse risk, with higher baseline levels correlating with increased relapse probability (p = 0.02 and p = 0.005) and longer time to achieve remission in multivariate LASSO models. These findings identify IL-17A and IL-10 as promising prognostic biomarkers for pediatric ALL, with potential application in risk stratification and guiding individualized treatment strategies.
{"title":"Serum cytokine profiling identifies IL-17A and IL-10 as prognostic biomarkers for disease outcome in pediatric acute lymphoblastic leukemia","authors":"Qian Ye , Jin Rao , Li Zhang , Muxia Yan , Huishan Chen , Yanping Yi , Hua Jiang , Xiaoliang Deng , Yiqian Wang","doi":"10.1016/j.clim.2025.110638","DOIUrl":"10.1016/j.clim.2025.110638","url":null,"abstract":"<div><div>Pediatric acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, yet reliable serum biomarkers for prognosis and relapse prediction remain limited. We profiled serum cytokines in 60 pediatric ALL patients and 19 healthy controls using the Aimplex Cytokine Assay, and evaluated predictive performance via receiver operating characteristic (ROC) analysis and least absolute shrinkage and selection operator (LASSO) regression. ALL patients exhibited significantly elevated levels of IFN-γ, IL-2, IL-4, IL-10, IL-17A, and TNF-α compared with controls. Among these, IL-17A and IL-10 showed the strongest associations with disease severity and relapse risk, with higher baseline levels correlating with increased relapse probability (<em>p</em> = 0.02 and <em>p</em> = 0.005) and longer time to achieve remission in multivariate LASSO models. These findings identify IL-17A and IL-10 as promising prognostic biomarkers for pediatric ALL, with potential application in risk stratification and guiding individualized treatment strategies.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110638"},"PeriodicalIF":3.8,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-05DOI: 10.1016/j.clim.2025.110637
Manfred Fliegauf , Kelly Nitschke , Pavla Mrovecova , Sara Posadas-Cantera , Nadezhda Camacho-Ordonez , Klaus Warnatz , Baerbel Keller , Bodo Grimbacher
Heterozygous pathogenic NFKB1 variants are one of the most frequent monogenic causes of disease in patients with inborn errors of immunity (IEI) and mainly compromise protein expression. NFKB1 encodes the precursor protein p105, which is processed into p50, the key transcription factor of canonical NF-κB1 signaling. Insufficiency of p105/p50 presents with immunodeficiency and autoinflammation.
Here, we evaluated two NFKB1 missense variants, identified in compound heterozygosity in cis (c.[150A>C;156A>C]; p.[Gln50His;Lys52Asn]) in a patient with immunodeficiency. While the isomorphic Q50H variant enhanced the rather marginal defect of K52N, the combination of both caused a pathogenic protein damage in p50. Our findings highlight an inherent challenge when analyzing single variants ‘isolated’ from their genetic context. Particularly when filtering out additional variants, e.g. based on allele frequencies, pathogenic effects originating from compound heterozygosity may be overlooked.
{"title":"Compound heterozygous NFKB1 missense variants in cis associated with immunodeficiency","authors":"Manfred Fliegauf , Kelly Nitschke , Pavla Mrovecova , Sara Posadas-Cantera , Nadezhda Camacho-Ordonez , Klaus Warnatz , Baerbel Keller , Bodo Grimbacher","doi":"10.1016/j.clim.2025.110637","DOIUrl":"10.1016/j.clim.2025.110637","url":null,"abstract":"<div><div>Heterozygous pathogenic <em>NFKB1</em> variants are one of the most frequent monogenic causes of disease in patients with inborn errors of immunity (IEI) and mainly compromise protein expression. <em>NFKB1</em> encodes the precursor protein p105, which is processed into p50, the key transcription factor of canonical NF-κB1 signaling. Insufficiency of p105/p50 presents with immunodeficiency and autoinflammation.</div><div>Here, we evaluated two <em>NFKB1</em> missense variants, identified in compound heterozygosity <em>in cis</em> (c.[150A>C;156A>C]; p.[Gln50His;Lys52Asn]) in a patient with immunodeficiency. While the isomorphic Q50H variant enhanced the rather marginal defect of K52N, the combination of both caused a pathogenic protein damage in p50. Our findings highlight an inherent challenge when analyzing single variants ‘isolated’ from their genetic context. Particularly when filtering out additional variants, <em>e.g.</em> based on allele frequencies, pathogenic effects originating from compound heterozygosity may be overlooked.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110637"},"PeriodicalIF":3.8,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145470831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Idiopathic inflammatory myopathies (IIMs) are autoimmune disorders characterized by muscle injury mediated by both T cells and macrophages. Ras guanyl-releasing protein 1 (RasGRP1) is a guanine exchange factor for a small G protein Ras, expressed in immune cells. In this study, we investigated the role of RasGRP1 in IIMs. RasGRP1 was expressed in either CD8+, CD4+ or CD68+ cells in muscles from IIM patients as well as a murine model of myositis, C protein-induced myositis (CIM). RasGRP1 expression was upregulated in activated CD8+ T cells and macrophages in vitro. Response to MHC Class I-restricted stimulation in Rasgrp1−/− CD8+ T cells was impaired. Furthermore, Rasgrp1−/− mice were resistant to CIM. Differentially expressed genes between Rasgrp1−/− and WT mice with CIM were enriched in both adaptive and innate immune responses. These results suggested that RasGRP1 could exacerbate myositis via both T cells and macrophages. RasGRP1 is a possible therapeutic target for IIMs.
{"title":"The exacerbating role of Ras guanyl-releasing protein 1 in idiopathic inflammatory myopathies","authors":"Marina Kise , Miku Shimamura , Natsuka Umezawa , Nao Tanaka , Rihan Da , Shiyao Li , Tadashi Hosoya , Tetsuya Saito , Chikashi Terao , Shinsuke Yasuda","doi":"10.1016/j.clim.2025.110636","DOIUrl":"10.1016/j.clim.2025.110636","url":null,"abstract":"<div><div>Idiopathic inflammatory myopathies (IIMs) are autoimmune disorders characterized by muscle injury mediated by both T cells and macrophages. Ras guanyl-releasing protein 1 (RasGRP1) is a guanine exchange factor for a small G protein Ras, expressed in immune cells. In this study, we investigated the role of RasGRP1 in IIMs. RasGRP1 was expressed in either CD8+, CD4+ or CD68+ cells in muscles from IIM patients as well as a murine model of myositis, C protein-induced myositis (CIM). RasGRP1 expression was upregulated in activated CD8+ T cells and macrophages <em>in vitro</em>. Response to MHC Class I-restricted stimulation in <em>Rasgrp1−/−</em> CD8+ T cells was impaired. Furthermore, <em>Rasgrp1−/−</em> mice were resistant to CIM. Differentially expressed genes between <em>Rasgrp1−/−</em> and WT mice with CIM were enriched in both adaptive and innate immune responses. These results suggested that RasGRP1 could exacerbate myositis <em>via</em> both T cells and macrophages. RasGRP1 is a possible therapeutic target for IIMs.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110636"},"PeriodicalIF":3.8,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.clim.2025.110633
Gabrielle Magdalena Tan , Kiran Sehmi , Sarah Azzi , Robert Hostoffer
Patients with primary or secondary immunodeficiencies are at an increased risk for recurrent respiratory infections despite standard intravenous immunoglobulin (IVIG) therapy. This retrospective quality improvement review evaluated the clinical impact of a high-titer IVIG product enriched with pathogen-specific antibodies in 14 patients after failing conventional IVIG. The primary outcomes were changes in infection frequency and hospitalization rates during the 6 months before and after treatment initiation, and from 6 months post-treatment to the present. Ten patients (71%) showed clinical improvement, with infections decreasing from 36 to 8 and hospitalizations from 14 to 5 in the first 6 months post-treatment; benefits were more pronounced when excluding one clinical outlier. Two patients discontinued therapy due to mild adverse effects or lack of efficacy. High-titer IVIG was associated with meaningful reductions in infection burden and hospitalizations, supporting its consideration for high-risk patients unresponsive to standard IVIG.
{"title":"High-titer IVIG 10 % (human)–slra reduces infections and hospitalizations over 6 to 12 months: A retrospective quality improvement study","authors":"Gabrielle Magdalena Tan , Kiran Sehmi , Sarah Azzi , Robert Hostoffer","doi":"10.1016/j.clim.2025.110633","DOIUrl":"10.1016/j.clim.2025.110633","url":null,"abstract":"<div><div>Patients with primary or secondary immunodeficiencies are at an increased risk for recurrent respiratory infections despite standard intravenous immunoglobulin (IVIG) therapy. This retrospective quality improvement review evaluated the clinical impact of a high-titer IVIG product enriched with pathogen-specific antibodies in 14 patients after failing conventional IVIG. The primary outcomes were changes in infection frequency and hospitalization rates during the 6 months before and after treatment initiation, and from 6 months post-treatment to the present. Ten patients (71%) showed clinical improvement, with infections decreasing from 36 to 8 and hospitalizations from 14 to 5 in the first 6 months post-treatment; benefits were more pronounced when excluding one clinical outlier. Two patients discontinued therapy due to mild adverse effects or lack of efficacy. High-titer IVIG was associated with meaningful reductions in infection burden and hospitalizations, supporting its consideration for high-risk patients unresponsive to standard IVIG.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110633"},"PeriodicalIF":3.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.clim.2025.110635
Erik Cimé-Aké , Guadalupe Lima , Emilio Godínez-Lazarini , Sandra Juárez , Hilda Marín-López , Daniela Flores-Hernández , Ileana Flores-Hernández , Amairani Gómez-Rodríguez , Diego F. Hernández-Ramírez , Luis Llorente , Hilda Fragoso-Loyo
The objective was to assess the expression of senescence and exhaustion markers in CD4+ and CD8+ T-cell subsets, along with the p16INK4a gene, in patients with systemic lupus erythematosus (SLE) and cognitive impairment (CI), compared with SLE patients without CI and healthy controls (HC). All participants underwent a standardized neurocognitive test battery, and CI was defined as performance ≥2 SD below the normative mean in ≥1 cognitive domain. The expression of immunosenescence and exhaustion markers was assessed by flow cytometry; expression of p16INK4a was assessed by qPCR. The SLE-CI group demonstrated a higher CD4+/CD8+ inverted ratio and increased p16INK4a expression. Compared with both SLE patients without CI and HC, SLE-CI patients exhibited reduced expression of CTLA-4+, LAG-3+, and PD-L1+ on CD4+ T-cells, as well as decreased PD-L1+ and TIM-3+ expression on CD8+ T-cells. Immunosenescence and T-cell exhaustion may contribute to the pathogenesis of CI in SLE.
{"title":"Immunosenescent and exhausted T cells in systemic lupus erythematosus patients with cognitive impairment","authors":"Erik Cimé-Aké , Guadalupe Lima , Emilio Godínez-Lazarini , Sandra Juárez , Hilda Marín-López , Daniela Flores-Hernández , Ileana Flores-Hernández , Amairani Gómez-Rodríguez , Diego F. Hernández-Ramírez , Luis Llorente , Hilda Fragoso-Loyo","doi":"10.1016/j.clim.2025.110635","DOIUrl":"10.1016/j.clim.2025.110635","url":null,"abstract":"<div><div>The objective was to assess the expression of senescence and exhaustion markers in CD4<sup>+</sup> and CD8<sup>+</sup> T-cell subsets, along with the p16<sup>INK4a</sup> gene, in patients with systemic lupus erythematosus (SLE) and cognitive impairment (CI), compared with SLE patients without CI and healthy controls (HC). All participants underwent a standardized neurocognitive test battery, and CI was defined as performance ≥2 SD below the normative mean in ≥1 cognitive domain. The expression of immunosenescence and exhaustion markers was assessed by flow cytometry; expression of p16<sup>INK4a</sup> was assessed by qPCR. The SLE-CI group demonstrated a higher CD4<sup>+</sup>/CD8<sup>+</sup> inverted ratio and increased p16<sup>INK4a</sup> expression. Compared with both SLE patients without CI and HC, SLE-CI patients exhibited reduced expression of CTLA-4<sup>+</sup>, LAG-3<sup>+</sup>, and PD-L1<sup>+</sup> on CD4<sup>+</sup> T-cells, as well as decreased PD-L1<sup>+</sup> and TIM-3<sup>+</sup> expression on CD8<sup>+</sup> T-cells. Immunosenescence and T-cell exhaustion may contribute to the pathogenesis of CI in SLE.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110635"},"PeriodicalIF":3.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-31DOI: 10.1016/j.clim.2025.110632
Maria Elena Maccari , Sven Kracker , Anita Chandra , Stephan Ehl , Markus G. Seidel , Joanne Tutein Nolthenius , Laura J. Clark , Jennifer Page , Annabel Griffiths , John Whalen
Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) is an ultra-rare, progressive disease characterised by immunodeficiency, immune dysregulation, and risk of malignancies. To further characterise the natural history of APDS, we analysed patient characteristics, manifestations, treatment use, and combinations of manifestations and combinations of treatments over time using longitudinal data from registration and follow-up visits in the European Society for Immunodeficiencies (ESID)-APDS registry. 140 patients were included (mean age: 17.7 years at registration; 19.1 years at last follow-up). Manifestation burden was high from childhood (patients experienced up to 9 manifestations by age 10). The number of treatments increased with age, with a 64 % probability of receiving ≥1 by age 10. Life-threatening APDS complications led to 13 deaths reported over 2.6 years' mean follow-up. These data highlight the chronic, progressive nature of APDS and its long-term impact on patients, with a high manifestation load and early mortality, despite widespread symptomatic treatment use.
{"title":"Natural history of clinical manifestations in activated phosphoinositide 3-kinase δ syndrome (APDS): Time-to-event analyses using the European Society for Immunodeficiencies-APDS registry","authors":"Maria Elena Maccari , Sven Kracker , Anita Chandra , Stephan Ehl , Markus G. Seidel , Joanne Tutein Nolthenius , Laura J. Clark , Jennifer Page , Annabel Griffiths , John Whalen","doi":"10.1016/j.clim.2025.110632","DOIUrl":"10.1016/j.clim.2025.110632","url":null,"abstract":"<div><div>Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) is an ultra-rare, progressive disease characterised by immunodeficiency, immune dysregulation, and risk of malignancies. To further characterise the natural history of APDS, we analysed patient characteristics, manifestations, treatment use, and combinations of manifestations and combinations of treatments over time using longitudinal data from registration and follow-up visits in the European Society for Immunodeficiencies (ESID)-APDS registry. 140 patients were included (mean age: 17.7 years at registration; 19.1 years at last follow-up). Manifestation burden was high from childhood (patients experienced up to 9 manifestations by age 10). The number of treatments increased with age, with a 64 % probability of receiving ≥1 by age 10. Life-threatening APDS complications led to 13 deaths reported over 2.6 years' mean follow-up. These data highlight the chronic, progressive nature of APDS and its long-term impact on patients, with a high manifestation load and early mortality, despite widespread symptomatic treatment use.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110632"},"PeriodicalIF":3.8,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mogamulizumab, an anti-CCR4 monoclonal antibody, is approved for relapsed/refractory (r/r) aggressive adult T-cell leukemia/lymphoma (ATL), although durable responses are limited.
Objective
To identify biomarkers associated with mogamulizumab efficacy, focusing on host immune status and known prognostic factors.
Methods
We retrospectively analyzed 315 patients with r/r aggressive ATL using real-world data from Japan. Clinical and prognostic variables were analyzed for association with overall survival (OS), stratified by mogamulizumab use.
Results
Among 315 patients, 97 received mogamulizumab (Moga [+]). One-year OS was higher in Moga (+) than Moga (−) patients (51.2 % vs. 34.0 %, p = 0.006). Multivariate analysis identified age < 70, PS 0–1, cCa < 11 mg/dL, albumin ≥3.5 g/dL, LDH < 265 IU/L, LMR ≥ 2.6, and Moga (+) use as independent predictors of OS. In Moga (+) patients, cCa and LMR remained independent prognostic factors.
Conclusion
LMR is a novel prognostic factor in r/r ATL and may provide useful information when considering mogamulizumab-based treatment.
背景：Mogamulizumab是一种抗ccr4单克隆抗体，被批准用于复发/难治性（r/r）侵袭性成人t细胞白血病/淋巴瘤（ATL），尽管持久的反应有限。目的：鉴定与mogamulizumab疗效相关的生物标志物，重点关注宿主免疫状态和已知预后因素。方法：我们回顾性分析了日本315例r/r侵袭性ATL患者的真实数据。分析临床和预后变量与总生存期（OS）的相关性，并按mogamulizumab的使用进行分层。结果：315例患者中，97例患者接受了mogamulizumab （Moga[+]）治疗。Moga（+）组1年OS高于Moga（-）组（51.2 % vs. 34.0 %,p = 0.006）。结论：LMR是r/r ATL的一个新的预后因素，在考虑莫加珠单抗治疗时可能提供有用的信息。
{"title":"Prognostic value of lymphocyte-to-monocyte ratio in relapsed/refractory adult T-cell Leukemia/lymphoma patients receiving mogamulizumab","authors":"Yutaka Shimazu , Takuro Kameda , Toshio Kitawaki , Ayako Kamiunten , Masaaki Sekine , Hiroshi Kawano , Seiichi Sato , Kouichi Maeda , Takanori Toyama , Noriaki Kawano , Kiyoshi Yamashita , Masanori Takeuchi , Junzo Ishizaki , Kazuya Shimoda , Akifumi Takaori-Kondo","doi":"10.1016/j.clim.2025.110616","DOIUrl":"10.1016/j.clim.2025.110616","url":null,"abstract":"<div><h3>Background</h3><div>Mogamulizumab, an anti-CCR4 monoclonal antibody, is approved for relapsed/refractory (r/r) aggressive adult T-cell leukemia/lymphoma (ATL), although durable responses are limited.</div></div><div><h3>Objective</h3><div>To identify biomarkers associated with mogamulizumab efficacy, focusing on host immune status and known prognostic factors.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 315 patients with r/r aggressive ATL using real-world data from Japan. Clinical and prognostic variables were analyzed for association with overall survival (OS), stratified by mogamulizumab use.</div></div><div><h3>Results</h3><div>Among 315 patients, 97 received mogamulizumab (Moga [+]). One-year OS was higher in Moga (+) than Moga (−) patients (51.2 % vs. 34.0 %, <em>p</em> = 0.006). Multivariate analysis identified age < 70, PS 0–1, cCa < 11 mg/dL, albumin ≥3.5 g/dL, LDH < 265 IU/L, LMR ≥ 2.6, and Moga (+) use as independent predictors of OS. In Moga (+) patients, cCa and LMR remained independent prognostic factors.</div></div><div><h3>Conclusion</h3><div>LMR is a novel prognostic factor in r/r ATL and may provide useful information when considering mogamulizumab-based treatment.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110616"},"PeriodicalIF":3.8,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-24DOI: 10.1016/j.clim.2025.110617
Lulu Zhang , Aichen Liu , Peiqi Yu , Jing Li , Xiaobin Cao , Yihao Liang , Wenke Sun , Songyun Ouyang , Liping Dai , Jingjing Liu
Autoantibodies against tumor-associated antigens (TAAs) in the plasma have demonstrated potential as biomarkers for cancer detection and prognosis. Copper transport proteins ATP7A and ATP7B (copper ATPase transporter α and β peptides, respectively), identified as TAAs, are abnormally expressed in patients with non-small cell lung cancer (NSCLC) and represent potential diagnostic biomarkers. In this study, we aimed to evaluate the diagnostic and prognostic values of plasma autoantibodies targeting ATP7A/B in NSCLC. The expression levels of anti-ATP7A/B autoantibodies were detected in a verification group of 75 patients with NSCLC and 75 normal controls (NC) and confirmed in a validation group including 253 patients with NSCLC, 253 patients with benign pulmonary nodules (BPN), and 253 NC using the enzyme-linked immunosorbent assay method. The results showed that the expression levels of anti-ATP7A/B autoantibodies in patients with NSCLC were significantly higher than in those with BPN and in NC. The anti-ATP7A/B autoantibodies distinguished NSCLC from NC with AUC values of 0.785 (95 % CI: 0.746–0.824) and 0.849 (95 % CI: 0.816–0.882), respectively. Those autoantibodies distinguished NSCLC from BPN with AUC values of 0.772 (95 % CI: 0.731–0.812) and 0.777 (95 % CI: 0.736–0.817), respectively. Additionally, the combination of anti-ATP7A and anti-ATP7B autoantibodies improved the efficacy of NSCLC diagnosis with increased AUC values. The prognostic values of anti-ATP7A/B autoantibodies were analyzed in 356 patients with NSCLC. The anti-ATP7B autoantibody served as an independent prognostic predictor for NSCLC, as high expression levels predicted poor prognosis. In conclusion, this study demonstrated the potential benefits of anti-ATP7A/B autoantibodies as biomarkers for NSCLC detection and prognosis.
{"title":"Plasma anti-ATP7A/B autoantibodies as potential biomarkers for the detection and prognosis of non-small cell lung cancer","authors":"Lulu Zhang , Aichen Liu , Peiqi Yu , Jing Li , Xiaobin Cao , Yihao Liang , Wenke Sun , Songyun Ouyang , Liping Dai , Jingjing Liu","doi":"10.1016/j.clim.2025.110617","DOIUrl":"10.1016/j.clim.2025.110617","url":null,"abstract":"<div><div>Autoantibodies against tumor-associated antigens (TAAs) in the plasma have demonstrated potential as biomarkers for cancer detection and prognosis. Copper transport proteins ATP7A and ATP7B (copper ATPase transporter α and β peptides, respectively), identified as TAAs, are abnormally expressed in patients with non-small cell lung cancer (NSCLC) and represent potential diagnostic biomarkers. In this study, we aimed to evaluate the diagnostic and prognostic values of plasma autoantibodies targeting ATP7A/B in NSCLC. The expression levels of anti-ATP7A/B autoantibodies were detected in a verification group of 75 patients with NSCLC and 75 normal controls (NC) and confirmed in a validation group including 253 patients with NSCLC, 253 patients with benign pulmonary nodules (BPN), and 253 NC using the enzyme-linked immunosorbent assay method. The results showed that the expression levels of anti-ATP7A/B autoantibodies in patients with NSCLC were significantly higher than in those with BPN and in NC. The anti-ATP7A/B autoantibodies distinguished NSCLC from NC with AUC values of 0.785 (95 % CI: 0.746–0.824) and 0.849 (95 % CI: 0.816–0.882), respectively. Those autoantibodies distinguished NSCLC from BPN with AUC values of 0.772 (95 % CI: 0.731–0.812) and 0.777 (95 % CI: 0.736–0.817), respectively. Additionally, the combination of anti-ATP7A and anti-ATP7B autoantibodies improved the efficacy of NSCLC diagnosis with increased AUC values. The prognostic values of anti-ATP7A/B autoantibodies were analyzed in 356 patients with NSCLC. The anti-ATP7B autoantibody served as an independent prognostic predictor for NSCLC, as high expression levels predicted poor prognosis. In conclusion, this study demonstrated the potential benefits of anti-ATP7A/B autoantibodies as biomarkers for NSCLC detection and prognosis.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110617"},"PeriodicalIF":3.8,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145414210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-24DOI: 10.1016/j.clim.2025.110615
Jinny Tsang , Avid Mohammadi , Sareh Bagherichimeh , Yoojin Choi , Azadeh Fazel , Elizabeth Tevlin , Sanja Huibner , Sara V. Good , Wangari Tharao , Bryan Coburn , Rupert Kaul
Elevated cervicovaginal cytokines/chemokines and epithelial disruption are associated with HIV risk. While penile-vaginal sex induces transient cervicovaginal inflammation and epithelial disruption, there is considerable interindividual heterogeneity. We defined genital inflammation using a multi-cytokine score and hypothesized that sex-induced inflammation would depend on the pre-existing vaginal immune milieu. We quantified HIV-associated immune factors in cervicovaginal secretions of HIV-uninfected women before and 1 h after penile-vaginal sex. Cervicovaginal IgA and IgG increased after sex, and baseline IgA was associated with inflammatory cytokines and epithelial disruption. Post-sex vaginal immune factors strongly associated and clustered with pre-sex concentrations, and participants with baseline inflammation remained inflamed after sex. Sex induced greater relative changes in inflammatory cytokines and epithelial disruption among participants with lower baseline levels, but not in chemokines. In conclusion, the baseline vaginal milieu determines the inflammatory effects of sex; specifically, sex elicits a greater change in inflammatory responses in women with baseline vaginal immunoquiescence.
{"title":"The baseline vaginal immune milieu is an important determinant of the inflammatory response induced by penile-vaginal sex","authors":"Jinny Tsang , Avid Mohammadi , Sareh Bagherichimeh , Yoojin Choi , Azadeh Fazel , Elizabeth Tevlin , Sanja Huibner , Sara V. Good , Wangari Tharao , Bryan Coburn , Rupert Kaul","doi":"10.1016/j.clim.2025.110615","DOIUrl":"10.1016/j.clim.2025.110615","url":null,"abstract":"<div><div>Elevated cervicovaginal cytokines/chemokines and epithelial disruption are associated with HIV risk. While penile-vaginal sex induces transient cervicovaginal inflammation and epithelial disruption, there is considerable interindividual heterogeneity. We defined genital inflammation using a multi-cytokine score and hypothesized that sex-induced inflammation would depend on the pre-existing vaginal immune milieu. We quantified HIV-associated immune factors in cervicovaginal secretions of HIV-uninfected women before and 1 h after penile-vaginal sex. Cervicovaginal IgA and IgG increased after sex, and baseline IgA was associated with inflammatory cytokines and epithelial disruption. Post-sex vaginal immune factors strongly associated and clustered with pre-sex concentrations, and participants with baseline inflammation remained inflamed after sex. Sex induced greater relative changes in inflammatory cytokines and epithelial disruption among participants with lower baseline levels, but not in chemokines. In conclusion, the baseline vaginal milieu determines the inflammatory effects of sex; specifically, sex elicits a greater change in inflammatory responses in women with baseline vaginal immunoquiescence.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110615"},"PeriodicalIF":3.8,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145463283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-21DOI: 10.1016/j.clim.2025.110610
Pauline Brevet , André Gillibert , Léna Le Goaréguer , Claire Lattard , Laurent Drouot , Rémi Varin , Marie-Laure Golinski , Sophie Candon , Olivier Boyer , Thierry Lequerré , Olivier Vittecoq , Manuel Fréret
Objective
Anti-modified protein antibodies (AMPA) are central in rheumatoid arthritis (RA). We evaluated whether changes in fine specificities (FS) of anti-citrullinated protein antibodies (ACPA) and anti-CarP antibodies relate to clinical prognosis in RA patients treated with abatacept (ABA) plus methotrexate (MTX).
Methods
A multiplex bead immunoassay measured 6 ACPA FS and 1 anti-CarP FS in 59 anti-CCP+ RA patients (IgG, IgA). Disease activity (DAS28-CRP) and FS levels were assessed at baseline (M0) and 6 months (M6).
Results
After 6 months of ABA+MTX, several FS decreased with frequent negative seroconversion (NS). Higher baseline anti-citrullinated α-enolase (ACit-ENO1) IgG levels predicted better outcome (decrease of −0.17 DAS28 score per decile, 95 % CI −0.27 to −0.07, p = 0.03). Among patients with ≥1 positive FS at M0, a higher number of NS across 14 FS (IgG/IgA) correlated with greater improvement (−0.27 DAS28 score per antibody, 95 % CI −0.39 to −0.15, p < 0.0001).
Conclusions
In this cohort of limited size, clinical response at M6 with ABA+MTX treatment was associated with the restriction of the autoantibody repertoire of IgG and IgA classes in RA patients.
目的：抗修饰蛋白抗体（AMPA）在类风湿关节炎（RA）中起中心作用。我们评估了抗瓜氨酸蛋白抗体（ACPA）和抗鲤鱼抗体的精细特异性（FS）变化是否与阿巴接受（ABA）加甲氨蝶呤（MTX）治疗的RA患者的临床预后有关。方法：采用多头免疫分析法检测59例抗ccp + RA患者（IgG、IgA）的6个ACPA FS和1个anti-CarP FS。在基线（M0）和6 个月（M6）时评估疾病活度（DAS28-CRP）和FS水平。结果：ABA+MTX治疗6 个月后，几个FS下降，血清转化阴性（NS）频繁发生。基线抗瓜氨酸α-烯醇化酶（ACit-ENO1） IgG水平越高，预后越好（DAS28评分每十分位数降低-0.17,95% % CI -0.27至-0.07,p = 0.03）。在M0≥1阳性FS的患者中，14个FS （IgG/IgA）中NS数量越多，改善程度越高（每个抗体DAS28评分-0.27,95% % CI -0.39至-0.15,p ）。结论：在这个规模有限的队列中，ABA+MTX治疗在M6时的临床反应与RA患者IgG和IgA类自身抗体库的限制有关。
{"title":"Autoantibody fine specificity restriction is associated with clinical response in RA treated with abatacept and methotrexate","authors":"Pauline Brevet , André Gillibert , Léna Le Goaréguer , Claire Lattard , Laurent Drouot , Rémi Varin , Marie-Laure Golinski , Sophie Candon , Olivier Boyer , Thierry Lequerré , Olivier Vittecoq , Manuel Fréret","doi":"10.1016/j.clim.2025.110610","DOIUrl":"10.1016/j.clim.2025.110610","url":null,"abstract":"<div><h3>Objective</h3><div>Anti-modified protein antibodies (AMPA) are central in rheumatoid arthritis (RA). We evaluated whether changes in fine specificities (FS) of anti-citrullinated protein antibodies (ACPA) and anti-CarP antibodies relate to clinical prognosis in RA patients treated with abatacept (ABA) plus methotrexate (MTX).</div></div><div><h3>Methods</h3><div>A multiplex bead immunoassay measured 6 ACPA FS and 1 anti-CarP FS in 59 anti-CCP+ RA patients (IgG, IgA). Disease activity (DAS28-CRP) and FS levels were assessed at baseline (M0) and 6 months (M6).</div></div><div><h3>Results</h3><div>After 6 months of ABA+MTX, several FS decreased with frequent negative seroconversion (NS). Higher baseline anti-citrullinated α-enolase (ACit-ENO1) IgG levels predicted better outcome (decrease of −0.17 DAS28 score per decile, 95 % CI −0.27 to −0.07, <em>p</em> = 0.03). Among patients with ≥1 positive FS at M0, a higher number of NS across 14 FS (IgG/IgA) correlated with greater improvement (−0.27 DAS28 score per antibody, 95 % CI −0.39 to −0.15, <em>p</em> < 0.0001).</div></div><div><h3>Conclusions</h3><div>In this cohort of limited size, clinical response at M6 with ABA+MTX treatment was associated with the restriction of the autoantibody repertoire of IgG and IgA classes in RA patients.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110610"},"PeriodicalIF":3.8,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号