Lewis J Williams, Connie SN Li-Wai-Suen, Alex L Garnham, Stefanie M Bader, Constantine S Tam, Ashley Whitechurch, Monica A Slavin, Marcel Doerflinger, Benjamin W Teh
{"title":"在高风险人群中阐明预测感染的新免疫特征：一项针对复发和难治性慢性淋巴细胞白血病患者的初步研究","authors":"Lewis J Williams, Connie SN Li-Wai-Suen, Alex L Garnham, Stefanie M Bader, Constantine S Tam, Ashley Whitechurch, Monica A Slavin, Marcel Doerflinger, Benjamin W Teh","doi":"10.1002/cti2.70049","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objectives</h3>\n \n <p>Chronic lymphocytic leukaemia (CLL) patients are at increased risk for infection, with the risk even higher for relapsed and refractory patients. Clinical assessment of infection risk is increasingly challenging in the era of immune-based therapies, such as Bruton's tyrosine kinase inhibitors. A pilot study was conducted to elucidate possible predictive immune markers.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Patients with relapsed and refractory CLL treated with ibrutinib were evaluated. Peripheral blood mononuclear cells (PBMCs) collected at defined intervals (baseline, 3- and 6 months following commencement of ibrutinib) were analysed, with or without phorbol myristate acetate (PMA)/ionomycin stimulation, using Luminex and RNA sequencing. Luminex and gene expression profiles were compared between patients that who did and did not develop infection to identify immune signatures associated with infection over a subsequent 3-month period.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Twenty-eight patients were included in this pilot study. Forty-six per cent of patients developed an infection (13 patients, 17 events) over 9 months of patient monitoring. Most infections were clinically diagnosed (72.7%) with the remainder microbiologically diagnosed bacterial (18.1%) and viral (9.2%) infections. Cell populations did not correlate with subsequent infection. An inflammatory transcriptome profile at 3 months following ibrutinib was associated with a subsequent infection episode. Increased whole protein response to PMA stimulation at 3 and 6 months was associated with subsequent risk for infections. Increased whole protein response to PMA stimulation was associated with subsequent risk of infection 3 months after commencing ibrutinib.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>The combination of protein and RNA analysis can provide further insight into the interactions of immunotherapies and immunity but should be validated further in large cohorts.</p>\n </section>\n </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 8","pages":""},"PeriodicalIF":3.8000,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70049","citationCount":"0","resultStr":"{\"title\":\"Elucidating novel immune profiles for predicting infection in high-risk cohorts: a pilot study in patients with relapsed and refractory chronic lymphocytic leukaemia\",\"authors\":\"Lewis J Williams, Connie SN Li-Wai-Suen, Alex L Garnham, Stefanie M Bader, Constantine S Tam, Ashley Whitechurch, Monica A Slavin, Marcel Doerflinger, Benjamin W Teh\",\"doi\":\"10.1002/cti2.70049\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objectives</h3>\\n \\n <p>Chronic lymphocytic leukaemia (CLL) patients are at increased risk for infection, with the risk even higher for relapsed and refractory patients. Clinical assessment of infection risk is increasingly challenging in the era of immune-based therapies, such as Bruton's tyrosine kinase inhibitors. A pilot study was conducted to elucidate possible predictive immune markers.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Patients with relapsed and refractory CLL treated with ibrutinib were evaluated. Peripheral blood mononuclear cells (PBMCs) collected at defined intervals (baseline, 3- and 6 months following commencement of ibrutinib) were analysed, with or without phorbol myristate acetate (PMA)/ionomycin stimulation, using Luminex and RNA sequencing. Luminex and gene expression profiles were compared between patients that who did and did not develop infection to identify immune signatures associated with infection over a subsequent 3-month period.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Twenty-eight patients were included in this pilot study. Forty-six per cent of patients developed an infection (13 patients, 17 events) over 9 months of patient monitoring. Most infections were clinically diagnosed (72.7%) with the remainder microbiologically diagnosed bacterial (18.1%) and viral (9.2%) infections. Cell populations did not correlate with subsequent infection. An inflammatory transcriptome profile at 3 months following ibrutinib was associated with a subsequent infection episode. Increased whole protein response to PMA stimulation at 3 and 6 months was associated with subsequent risk for infections. Increased whole protein response to PMA stimulation was associated with subsequent risk of infection 3 months after commencing ibrutinib.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>The combination of protein and RNA analysis can provide further insight into the interactions of immunotherapies and immunity but should be validated further in large cohorts.</p>\\n </section>\\n </div>\",\"PeriodicalId\":152,\"journal\":{\"name\":\"Clinical & Translational Immunology\",\"volume\":\"14 8\",\"pages\":\"\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2025-08-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70049\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical & Translational Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/cti2.70049\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical & Translational Immunology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cti2.70049","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Elucidating novel immune profiles for predicting infection in high-risk cohorts: a pilot study in patients with relapsed and refractory chronic lymphocytic leukaemia
Objectives
Chronic lymphocytic leukaemia (CLL) patients are at increased risk for infection, with the risk even higher for relapsed and refractory patients. Clinical assessment of infection risk is increasingly challenging in the era of immune-based therapies, such as Bruton's tyrosine kinase inhibitors. A pilot study was conducted to elucidate possible predictive immune markers.
Methods
Patients with relapsed and refractory CLL treated with ibrutinib were evaluated. Peripheral blood mononuclear cells (PBMCs) collected at defined intervals (baseline, 3- and 6 months following commencement of ibrutinib) were analysed, with or without phorbol myristate acetate (PMA)/ionomycin stimulation, using Luminex and RNA sequencing. Luminex and gene expression profiles were compared between patients that who did and did not develop infection to identify immune signatures associated with infection over a subsequent 3-month period.
Results
Twenty-eight patients were included in this pilot study. Forty-six per cent of patients developed an infection (13 patients, 17 events) over 9 months of patient monitoring. Most infections were clinically diagnosed (72.7%) with the remainder microbiologically diagnosed bacterial (18.1%) and viral (9.2%) infections. Cell populations did not correlate with subsequent infection. An inflammatory transcriptome profile at 3 months following ibrutinib was associated with a subsequent infection episode. Increased whole protein response to PMA stimulation at 3 and 6 months was associated with subsequent risk for infections. Increased whole protein response to PMA stimulation was associated with subsequent risk of infection 3 months after commencing ibrutinib.
Conclusion
The combination of protein and RNA analysis can provide further insight into the interactions of immunotherapies and immunity but should be validated further in large cohorts.
期刊介绍：
Clinical & Translational Immunology is an open access, fully peer-reviewed journal devoted to publishing cutting-edge advances in biomedical research for scientists and physicians. The Journal covers fields including cancer biology, cardiovascular research, gene therapy, immunology, vaccine development and disease pathogenesis and therapy at the earliest phases of investigation.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
