Caroline Mangare, Sabine Tischer-Zimmermann, Agnes Bonifacius, Sebastian B. Riese, A. Dragon, R. Blasczyk, B. Maecker-Kolhoff, B. Eiz-Vesper
{"title":"Variances in Antiviral Memory T-Cell Repertoire of CD45RA- and CD62L-Depleted Lymphocyte Products Reflect the Need of Individual T-Cell Selection Strategies to Reduce the Risk of GvHD while Preserving Antiviral Immunity in Adoptive T-Cell Therapy","authors":"Caroline Mangare, Sabine Tischer-Zimmermann, Agnes Bonifacius, Sebastian B. Riese, A. Dragon, R. Blasczyk, B. Maecker-Kolhoff, B. Eiz-Vesper","doi":"10.1159/000516284","DOIUrl":"https://doi.org/10.1159/000516284","url":null,"abstract":"Introduction: Viral infections and reactivations still remain a cause of morbidity and mortality after hematopoietic stem cell transplantation due to immunodeficiency and immunosuppression. Transfer of unmanipulated donor-derived lymphocytes (DLI) represents a promising strategy for improving cellular immunity but carries the risk of graft versus host disease (GvHD). Depleting alloreactive naïve T cells (TN) from DLIs was implemented to reduce the risk of GvHD induction while preserving antiviral memory T-cell activity. Here, we compared two TN depletion strategies via CD45RA and CD62L expression and investigated the presence of antiviral memory T cells against human adenovirus (AdV) and Epstein-Barr virus (EBV) in the depleted fractions in relation to their functional and immunophenotypic characteristics. Methods: T-cell responses against ppEBV_EBNA1, ppEBV_Consensus and ppAdV_Hexon within TN-depleted (CD45RA−/CD62L−) and TN-enriched (CD45RA+/CD62L+) fractions were quantified by interferon-gamma (IFN-γ) ELISpot assay after short- and long-term in vitro stimulation. T-cell frequencies and immunophenotypic composition were assessed in all fractions by flow cytometry. Moreover, alloimmune T-cell responses were evaluated by mixed lymphocyte reaction. Results: According to differences in the phenotype composition, antigen-specific T-cell responses in CD45RA− fraction were up to 2 times higher than those in the CD62L− fraction, with the highest increase (up to 4-fold) observed after 7 days for ppEBV_EBNA1-specific T cells. The CD4+ effector memory T cells (TEM) were mainly responsible for EBV_EBNA1- and AdV_Hexon-specific T-cell responses, whereas the main functionally active T cells against ppEBV_Consensus were CD8+ central memory T cells (TCM) and TEM. Moreover, comparison of both depletion strategies indicated that alloreactivity in CD45RA− was lower than that in CD62L− fraction. Conclusion: Taken together, our results indicate that CD45RA depletion is a more suitable strategy for generating TN-depleted products consisting of memory T cells against ppEBV_EBNA1 and ppAdV_Hexon than CD62L in terms of depletion effectiveness, T-cell functionality and alloreactivity. To maximally exploit the beneficial effects mediated by antiviral memory T cells in TN-depleted products, depletion methods should be selected individually according to phenotype composition and CD4/CD8 antigen restriction. TN-depleted DLIs may improve the clinical outcome in terms of infections, GvHD, and disease relapse if selection of pathogen-specific donor T cells is not available.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"49 1","pages":"30 - 43"},"PeriodicalIF":2.2,"publicationDate":"2021-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45129966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Front & Back Matter","authors":"N. Worel, Wien · Österreich, Gregor Bein","doi":"10.1159/000519477","DOIUrl":"https://doi.org/10.1159/000519477","url":null,"abstract":"S ISBN 978–3–318–06907–5 48 | S1 | 21 K ager Trafusion M eicine nd H em oterapy |","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47171128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"54. Jahrestagung der Deutschen Gesellschaft für Transfusionsmedizin und Immunhämatologie (DGTI), 22.–24. September 2021, DIGITAL, Abstracts","authors":"","doi":"10.1159/000518751","DOIUrl":"https://doi.org/10.1159/000518751","url":null,"abstract":"","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"48 1","pages":"1 - 79"},"PeriodicalIF":2.2,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47392746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Vorspann","authors":"","doi":"10.11129/9783955535070-001","DOIUrl":"https://doi.org/10.11129/9783955535070-001","url":null,"abstract":"","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"48 1","pages":"I - II"},"PeriodicalIF":2.2,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46680508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tae Yeul Kim, HongBi Yu, M. Phan, Ja-Hyun Jang, D. Cho
{"title":"Application of Blood Group Genotyping by Next-Generation Sequencing in Various Immunohaematology Cases","authors":"Tae Yeul Kim, HongBi Yu, M. Phan, Ja-Hyun Jang, D. Cho","doi":"10.1159/000517565","DOIUrl":"https://doi.org/10.1159/000517565","url":null,"abstract":"Background: Next-generation sequencing (NGS) technology has been recently introduced into blood group genotyping; however, there are few studies using NGS-based blood group genotyping in real-world clinical settings. In this study, we applied NGS-based blood group genotyping into various immunohaematology cases encountered in routine clinical practice. Methods: This study included 4 immunohaematology cases: ABO subgroup, ABO chimerism, antibody to a high-frequency antigen (HFA), and anti-CD47 interference. We designed a hybridization capture-based NGS panel targeting 39 blood group-related genes and applied it to the 4 cases. Results: NGS analysis revealed a novel intronic variant (NM_020469.3:c.29-10T>G) in a patient with an Ael phenotype and detected a small fraction of ABO*A1.02 (approximately 3–6%) coexisting with the major genotype ABO*B.01/O.01.02 in dizygotic twins. In addition, NGS analysis found a homozygous stop-gain variant (NM_004827.3:c.376C>T, p.Gln126*; ABCG2*01N.01) in a patient with an antibody to an HFA; consequently, this patient’s phenotype was predicted as Jr(a−). Lastly, blood group phenotypes predicted by NGS were concordant with those determined by serology in 2 patients treated with anti-CD47 drugs. Conclusion: NGS-based blood group genotyping can be used for identifying ABO subgroup alleles, low levels of blood group chimerism, and antibodies to HFAs. Furthermore, it can be applied to extended blood group antigen matching for patients treated with anti-CD47 drugs.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"49 1","pages":"88 - 97"},"PeriodicalIF":2.2,"publicationDate":"2021-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41655006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Front & Back Matter","authors":"G. Bein","doi":"10.1159/000518831","DOIUrl":"https://doi.org/10.1159/000518831","url":null,"abstract":"","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48216001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Front & Back Matter","authors":"G. Bein","doi":"10.1159/000517497","DOIUrl":"https://doi.org/10.1159/000517497","url":null,"abstract":"","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48230589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"PharmaNews","authors":"","doi":"10.1159/000516082","DOIUrl":"https://doi.org/10.1159/000516082","url":null,"abstract":"Die Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie (DGHO) hat die Leitlinie für die Diagnose und Therapie der Immunthrombozytopenie (ITP) aktualisiert. Fostamatinib (Tavlesse®) wird nun als Zweitlinientherapie zur Behandlung der ITP empfohlen [1]. Der Wirkstoff inhibiert zielgerichtet SYK (spleen tyrosine kinase), die zur Gruppe der zytoplasmatischen Tyrosinkinasen gehört. Diese Kinasen spielen in der Pathogenese der ITP eine Schlüsselrolle. Mit seinem neuartigen Wirkmechanismus greift Fostamatinib gezielt in die Pathophysiologie der ITP ein und hemmt zielgerichtet den unphysiologischen Abbau der Thrombozyten [2]. Seit Juli 2020 ist Tavlesse® in Deutschland verfügbar. Es ist zugelassen zur Behandlung der chronischen ITP bei erwachsenen Patienten, die gegenüber anderen Behandlungsarten therapieresistent sind [3]. Die Empfehlung als Zweitlinientherapie ist insbesondere von Interesse, da Studien eine besonders gute Wirksamkeit beim Einsatz in dieser Therapielinie zeigen [4]. Die empfohlene initiale Dosis beträgt 100 mg 2-mal täglich. Über 80% der Patienten wurden in den Zulassungsstudien auf 150 mg 2-mal täglich eingestellt. Tavlesse® wird oral und nahrungsunabhängig eingenommen [3].","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"48 1","pages":"134 - 136"},"PeriodicalIF":2.2,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000516082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48198288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hämophilie A: Emicizumab-Prophylaxe zeigt hohe Therapieadhärenz","authors":"","doi":"10.1159/000516081","DOIUrl":"https://doi.org/10.1159/000516081","url":null,"abstract":"","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":" ","pages":"I - II"},"PeriodicalIF":2.2,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000516081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48215911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Front & Back Matter","authors":"G. Bein","doi":"10.1159/000516223","DOIUrl":"https://doi.org/10.1159/000516223","url":null,"abstract":"","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"1 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41404256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}