Multi-dimensional CSF Flow Cytometry for Neuro-inflammatory Disease Stratification
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Solution Overview
Problem
Current methods for diagnosing neurological or psychiatric diseases, particularly neuro-inflammatory autoimmune diseases, are inadequate as they rely on costly differential diagnoses and lack sensitive and specific markers for stratification.
Innovation Solution
A method involving the determination of specific cell levels in cerebrospinal fluid (CSF) and peripheral blood (PB) samples, including B cells, immune cells, NKT cells, monocytes, and CD56 dim< CD16 +< NK cells, to stratify subjects with neuro-inflammatory autoimmune diseases based on increased or decreased levels relative to control samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional CSF parameters (total cell counts, lactate, protein) are used for diagnosis, then the diagnostic process is simple and quick, but the measurement precision and ability to distinguish between similar disease entities is insufficient
Solution Approach 1:
The patent transitions from conventional single-parameter CSF analysis to multi-dimensional flow cytometry analysis by adding multiple new dimensions of measurement. Specifically, it introduces 13 new flow cytometry parameters including total leukocyte count, differential leukocyte counts (lymphocytes, monocytes, granulocytes), and plasma cell counts, transforming the diagnostic approach from one-dimensional to multi-dimensional characterization of CSF immune cells
Solution Approach 2:
The patent segments the immune cell population into distinct subsets for individual analysis. Instead of measuring total cell counts only, it divides and measures specific cell types separately: lymphocytes, monocytes, granulocytes, and plasma cells. This segmentation allows precise identification of disease-specific patterns in different cell populations, improving diagnostic precision for distinguishing between neuro-inflammatory, neuro-degenerative, and neuro-vascular diseases
2Measurement precision
If multi-parameter flow cytometry analysis is performed on CSF, then the diagnostic precision and disease stratification capability is improved, but the cost and complexity of the diagnostic process increases
Solution Approach 1:
The patent creates a universal multi-functional diagnostic panel that can identify and differentiate multiple disease categories (neuro-inflammatory, neuro-degenerative, neuro-vascular) and specific diseases within each category (MS, ALS, Alzheimer's, stroke, etc.) using a single integrated flow cytometry analysis. This universal approach eliminates the need for separate specialized tests for different disease types, making the enhanced diagnostic capability broadly applicable across neurological disorders
Solution Approach 2:
The patent establishes specific quantitative parameter thresholds and patterns for disease identification. It defines characteristic patterns such as increased plasma cell counts in neuro-inflammatory diseases, specific lymphocyte-to-monocyte ratios in different disease categories, and quantitative thresholds for total leukocyte counts. These parameter changes transform the flow cytometry data into actionable diagnostic criteria that guide disease stratification
3Measurement precision
If costly differential diagnosis methods are used to distinguish between neurological diseases, then the diagnostic accuracy is improved, but the loss of time and economic resources increases
Solution Approach 1:
The patent performs preliminary disease categorization and stratification through the initial flow cytometry analysis of CSF immune cell parameters. By establishing specific parameter patterns and thresholds in advance (such as plasma cell count thresholds for neuro-inflammatory diseases, or lymphocyte-to-monocyte ratios for differentiating disease categories), the system enables rapid initial diagnosis that guides subsequent clinical decisions, avoiding the need for lengthy sequential differential diagnosis procedures
Data Source
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AI summary
The present invention relates to a method of stratifying a subject with neurological or psychiatric disease manifestation, preferably with neuro-inflammatory autoimmune diseases a) determining i) a level of B cells in a test cerebrospinal fluid (CSF) sample obtained from a subject; ii) a level of immune cells per μl in said test CSF sample obtained from said subject; iii) a level of NKT cells in said test CSF sample obtained from said subject; iv) a level of monocytes in said test CSF sample obtained from said subject, and v) a level of CD56dim CD16+ NK cells in a test peripheral blood (PB) sample obtained from said subject, and b) stratifying said subject as suffering from neuro-inflammatory autoimmune diseases, if the following are fulfilled: i) the level of B cells is increased relative to corresponding levels of B cells in control CSF samples obtained from subjects not suffering from neuro-inflammatory autoimmune diseases; ii) the level of immune cells per μl is increased relative to corresponding levels of immune cells per μl in said control CSF samples obtained from said subjects not suffering from neuro-inflammatory autoimmune diseases; iii) the level of NKT cells is decreased relative to corresponding levels of NKT cells in said control CSF samples obtained from said subjects not suffering from neuro- inflammatory autoimmune diseases; iv) the level of monocytes is decreased relative to corresponding levels of monocytes in said control CSF samples obtained from said subjects not suffering from neuro-inflammatory autoimmune diseases; v) the level of CD56dim CD16+ NK cells is decreased relative to corresponding levels of CD56dim CD16+ NK cells in control PB samples obtained from said subjects not suffering from neuro-inflammatory autoimmune diseases, wherein the combination of said levels i) - v) of step b) is indicative for whether said subject is suspected to suffer from neuro-inflammatory autoimmune diseases or from another neurological or psychiatric disease manifestation other than neuro-inflammatory autoimmune disease. Further, the present invention relates to a data processing system comprising a processor configured to perform the method of the invention, a flow cytometry device capable of detecting the abovementioned levels and a computer program comprising instructions to cause the data processing system or the flow cytometry device to execute the steps of the method of the invention. Finally, the present invention relates to a kit comprising a fluorescently labeled binding partner for certain surface markers used in the method of the invention.