P307 FMT-associated alterations in the TCR repertoire of patients with severe or fulminant clostridioides difficile infection
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".