| Autor: |
Brandi Roach, Tanya Monaghan, Dina Kao, Karen Wong, Benjamin H. Mullish, Elisa Rosati, Christos Polytarchou, Julian Marchesi, Gane Ka-Shu Wong, Andre Franke, Lindsey Russell |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Posters. |
| Popis: |
Introduction The adaptive immune system is important in modulating disease outcomes in Clostridioides difficile infection (CDI). Herein, we sought to characterize the TCRα and TCRβ repertoire in peripheral blood mononuclear cells (PBMCs) pre- and post-sequential Faecal Transplantation (FMT) for the treatment of patients with severe or fulminant CDI. Methods Three patients were included in the study: 1 patient had fulminant CDI with shock while 2 patients had severe CDI. Each cycle of treatment consisted of daily FMT by enema for 3 days plus fidaxomicin 200 mg PO BID for 7–10 days. Samples were collected every 5 days over a period of 4 weeks, then at 6 weeks. Two patients had resolution of diarrhoea 2 weeks following 2 treatment cycles. Two different FMT donor samples were also analysed. Total RNA isolated from PBMCs was used for TCR library preparation using unique molecular identifiers (UMIs). Samples underwent targeted cDNA synthesis, using primers for the constant region of TCRα and TCRβ chains. Libraries were sequenced on Illumina NovaSeq6000. Data pre-processing was conducted using the MIGEC and MIXCR software. We analysed repertoire clonality over time and temporal clonal abundance trajectories of specific TCRs during treatment. Results The 2 FMT donors displayed lower clonality compared to all 3 CDI patients. Both treatment responders exhibited stable clonality profiles over time. In the non-responder (fulminant CDI), clonality was much higher pre-FMT and drastically decreased following the first cycle of FMT when diarrhoea resolved transiently. However, following TCR clustering based on temporal trajectories, a significant increase in relative abundance of specific clonotypes was observed at the end of FMT cycle 2 when CDI recurred. Temporal clustering analyses also revealed clonotypes which strongly decreased or increased over time in concomitance with positive response to FMT, suggesting an association with CDI progression and remission. Conclusions This is the first attempt to assess the potential of TCR repertoire profiling as a prognostic tool for assessing clinical outcomes of FMT in severe or fulminant CDI and of evaluating the role that specific T cell clonotypes may play in mediating FMT efficacy. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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