F. prausnitzii-Specific DP8a Cell Detection for Noninvasive IBD Assessment
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Solution Overview
Problem
Existing methods for diagnosing, prognosing, and treating inflammatory bowel diseases (IBD) related to a decrease in Faecalibacterium prausnitzii are cumbersome, invasive, and require culturing the bacterium, which is difficult due to its anaerobic properties and necessitate autologous or HLA-matched antigen presenting cells.
Innovation Solution
The use of CCR6 and CXCR6 markers to select Faecalibacterium prausnitzii-specific DP8a cells from a blood sample, allowing non-invasive, reliable, and easy assessment of colonic homeostasis or inflammation status without the need for culturing or autologous antigen presenting cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional methods are used to select and quantify F. prau-specific DP8a cells, then diagnostic accuracy is improved, but the process becomes cumbersome and requires complex culturing procedures
Solution Approach 1:
The invention extracts the essential identifying features (CCR6 and CXCR6 markers) from the complex F. prau-specific DP8a cell selection process. By focusing on these specific surface markers rather than requiring full functional assessment through culturing, the method simplifies the diagnostic workflow while maintaining accuracy in identifying the regulatory T cell population specific to F. prausnitzii
Solution Approach 2:
The invention performs preliminary identification of F. prau-specific DP8a cells using CCR6 and CXCR6 marker expression as a proxy for full specificity. This preliminary action allows clinicians to identify and quantify the relevant cell population without completing the entire culturing and functional assessment process, thereby reducing time and complexity while maintaining diagnostic utility
2Reliability
If F. prau culturing is performed to identify specific DP8a cells, then cell specificity is improved, but the procedure becomes time-consuming and technically difficult
Solution Approach 1:
The invention replaces the mechanical culturing process with a molecular marker-based identification system. Instead of physically cultivating F. prau and observing DP8a cell responses, the method uses flow cytometry or similar techniques to detect CCR6 and CXCR6 marker expression on DP8a cells, substituting a time-intensive biological process with a faster molecular detection approach
Solution Approach 2:
The invention introduces CCR6 and CXCR6 markers as intermediary indicators of F. prau-specificity. These markers serve as proxies that correlate with true F. prau reactivity without requiring direct interaction with the bacterium. The markers mediate the identification process, allowing inference of cell specificity through marker expression patterns rather than direct functional assessment
3Measurement precision
If autologous or HLA-matched antigen presenting cells are used, then diagnostic accuracy is improved, but the procedure becomes more invasive and complex
Solution Approach 1:
The invention makes the diagnostic approach universal by using CCR6 and CXCR6 markers that are constitutively expressed on F. prau-specific DP8a cells regardless of the patient's HLA type or other individual variations. This universal marker system eliminates the need for patient-specific customization of antigen-presenting cells, allowing the same diagnostic protocol to be applied across diverse patient populations
Solution Approach 2:
The invention uses surface marker expression patterns as a copy or proxy for the more complex autologous cell-based assays. Rather than requiring the actual autologous antigen-presenting cells and their specific interactions, the method copies the essential identifying feature (marker expression) that would result from such interactions, providing a simplified but accurate alternative
Data Source
AI summary
The invention relates to a method comprising a step of determining the number, concentration and/or proportion of T lymphocytes with a CD4+ CD8ααlow phenotype and further expressing CCR6 and/or CXCR6, for (i) diagnosing, (ii) prognosing outcome of, or (iii) predicting the risk of developing a disease related to a decrease of F. prau. The invention also concerns the treatment of said disease by administering a population of these specific T lymphocytes. The Inventors have indeed identified two markers, CCR6 and CXCR6, enabling to select a population of F. prau-specific cells among CD4+ CD8ααlow T lymphocytes, from a blood sample and without needing to assess their F. prau specificity. T lymphocytes with a CD4+ CD8ααlow CCR6+ CXCR6+ phenotype are for example significantly decreased in IBD patients. The disease related to a decrease of F. prau is particularly an inflammatory bowel disease (IBD), such as Crohn's disease.