MAIT and iNKT Cell Quantification for Type 1 Diabetes Risk Assessment
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Solution Overview
Problem
Current methods for assessing the status, risk, or prognosis of type 1 diabetes are inadequate, particularly in identifying individuals at risk or determining the progression of the disease, as they do not effectively account for the role of gut microbiota and innate-like T-cells such as MAIT and iNKT cells in immune modulation.
Innovation Solution
A method involving the quantification of MAIT and iNKT cells in blood samples, comparing the quantification values to predetermined reference values, and analyzing specific markers like CCR6, CD25, CD56, PD1, and others to determine the risk or presence of type 1 diabetes, utilizing flow cytometry for accurate cell population analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional methods are used to assess type 1 diabetes risk, then the assessment can be performed with standard procedures, but the accuracy and ability to identify individuals at risk is insufficient
Solution Approach 1:
The patent segments the immune system assessment into distinct cell population categories (MAIT cells, iNKT cells, and other T-cell subsets), allowing for targeted quantification of specific immune components that are most relevant to type 1 diabetes risk. This segmentation enables precise measurement of disease-associated immune parameters without requiring complete analysis of all immune cells.
Solution Approach 2:
The patent uses flow cytometry as an intermediary technology to bridge the gap between conventional assessment methods and the need for precise immune cell quantification. Flow cytometry serves as a mediator that can simultaneously measure multiple cell surface markers and differentiate between various T-cell populations, providing accurate risk assessment while maintaining operational feasibility.
2Reliability
If the assessment method focuses on specific cell populations like MAIT and iNKT cells, then the risk identification accuracy improves, but the measurement and detection difficulty increases
Solution Approach 1:
The patent employs fluorescently labeled antibodies that bind to specific cell surface markers on MAIT and iNKT cells. These fluorescent labels emit different colors or wavelengths when excited, allowing for visual and instrumental differentiation of target cell populations from other immune cells. This color-based detection method significantly reduces the difficulty of identifying and quantifying rare T-cell subsets.
Solution Approach 2:
The patent replaces manual cell counting and morphological identification with flow cytometry, an automated instrumental system. This substitution eliminates the need for labor-intensive manual analysis and provides objective, reproducible quantification of cell populations based on their physical and optical properties, thereby reducing measurement difficulty while improving reliability.
3Loss of information
If comprehensive cell marker analysis is performed, then the prognostic information obtained is more detailed, but the time and resources required increase
Solution Approach 1:
The patent utilizes flow cytometry's capability to analyze multiple parameters simultaneously in a continuous process. The instrument can measure multiple cell surface markers, intracellular markers, and functional properties of the same cell population in a single uninterrupted run, eliminating the need for sequential analysis methods that would be time-consuming and lose cellular integrity between measurements.
Solution Approach 2:
The patent combines the quantification of multiple T-cell populations (MAIT cells, iNKT cells, and other subsets) and their various markers into a single integrated assessment protocol. This merging of multiple measurement tasks into one unified flow cytometry experiment reduces the total time required while maintaining comprehensive prognostic information, as all measurements are performed on the same sample under identical conditions.
Data Source
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AI summary
The present invention relates to methods and kits of assessing status, risk or prognosis of type 1 diabetes. There is still a need for improved methods of prognosis of type 1 diabetes. The inventors have observed different alterations of iNKT and MAIT cells quantity, frequency and markers in T1D patients compared to controls and also in children with recent onset T1D compared to control children or children with established T1D. The present invention relates to a method of assessing status, risk or prognosis of type 1 diabetes in a subject comprising i) quantifying at least one population of innate-like T-cells in a blood sample obtained from the subject, ii) comparing the quantification value determined at step i) with a predetermined reference value and iii) detecting differential in the quantification value determined at step i) and the predetermined reference value is indicative of the status, risk of prognosis of type 1 diabetes.