CN-121995053-A - Inflammation marker and application thereof

Abstract

The invention discloses an inflammation marker and application thereof. The invention reveals the application potential of TKFC in inflammation detection for the first time, finds TKFC expression condition on cell membranes based on immune cells, can accurately judge immune cell states and/or organism inflammation conditions, and provides a new technical means for accurate identification and monitoring of inflammation.

Inventors

• WEI YUANAN
• LI YUEMING
• HUANG HUAYONG

Assignees

• 广东凯安生命技术有限公司

Dates

Publication Date

20260508

Application Date

20260112

Claims (14)

1. 1. Use of a triple kinase/FMN cyclase (TKFC) on the cell membrane of an immune cell as an immune cell surface marker for characterizing immune cell status and/or inflammatory conditions of the body; Wherein the immune cell state comprises a resting state and an activated state; the body inflammatory conditions include the presence of inflammation and/or the extent of occurrence of inflammation.
2. 2. The use according to claim 1, wherein the immune cells comprise white blood cells; preferably, the white blood cells comprise myeloid cells; preferably, the leukocytes comprise monocytes, granulocytes.
3. 3. The use according to claim 1, wherein the immune cells further comprise macrophages, dendritic cells and mast cells.
4. 4. The use according to claim 2 or 3, wherein the immune cells are derived from an animal; preferably, the animal is a vertebrate; Preferably, the vertebrates include human and non-human mammals.
5. 5. The use according to claim 1, wherein the inflammation comprises systemic inflammation and local inflammation.
6. 6. The use according to claim 1, wherein the inflammation is pathogen-induced inflammation; preferably, the pathogen comprises at least one of bacteria, fungi, viruses, parasites, mycoplasma, chlamydia, rickettsia, prions.
7. 7. Use of a substance that detects TKFC on the cell membrane of an immune cell for the preparation of a product for diagnosing inflammation; preferably, the detection comprises a quantitative and/or qualitative detection; Preferably, the product comprises a detection reagent, a detection kit and a detection chip.
8. 8. The use according to claim 7, wherein the substance is capable of effecting detection of TKFC on the cell membrane of an immune cell based on at least one of the following methods: Fluorescence microscopy imaging techniques, immunohistochemical methods, flow cytometry, western blotting, enzyme-linked immunosorbent, mass spectrometry, radioligand binding, CRISPR-based labeling techniques; Preferably, the method does not include the step of lysing or disrupting the immune cells.
9. 9. The use according to claim 7, wherein the substance comprises an antibody; Preferably, the antibody comprises an anti-TKFC monoclonal antibody.
10. 10. The use according to any one of claims 7 to 9, wherein the product further comprises a substance for detecting an immunocompetent factor and/or an immunocytomarker; preferably, the immunocompetent factors comprise immunocytokines; preferably, the immune cytokine comprises interferon-gamma; Preferably, the immune cell markers comprise cluster of differentiation (‌ CD) proteins.
11. 11. The use of claim 10, wherein the test sample of the product comprises at least one of peripheral blood, pleural effusion, ascites, cerebrospinal fluid and other tissue exudates.
12. 12. Use of a substance that detects TKFC on the cell membrane of an immune cell for the preparation of a product that characterizes the state of the immune cell.
13. 13. A method of characterizing immune cell status, comprising: Detecting TKFC expression on the cell membrane of the immune cell, and judging the state of the immune cell by comparing TKFC expression difference on the resting immune cell; Preferably, the resting immune cells comprise immune cells derived from a healthy human or a non-inflammatory patient.
14. 14. The method of claim 13, wherein the criteria for determining immune cell status are: When the expression level of TKFC on the cell membrane of the immune cell to be detected is higher than the baseline level, the immune cell to be detected is an activated immune cell, and when the expression level is equal to or lower than the baseline level of the immune cell to be detected, the immune cell to be detected is a resting immune cell; Preferably, the baseline comprises a level of TKFC expressed on the cell membrane of leukocytes of a non-inflammatory patient; Preferably, the non-inflammatory patient comprises a healthy person.

Description

Inflammation marker and application thereof Technical Field The invention relates to the technical field of biomarkers, in particular to an inflammation marker and application thereof. Background Inflammation is a complex physiological and pathological response generated when the organism responds to infection, injury or abnormal stimulus, and is widely involved in the occurrence, development and prognosis of various diseases. Inflammation plays a key role in both infectious diseases (e.g., pneumonia, sepsis) and non-infectious diseases (e.g., atherosclerosis, rheumatoid arthritis, tumors, etc.). Therefore, the method can timely and accurately detect the inflammatory state, and has important significance for early diagnosis of diseases, treatment strategy formulation and curative effect monitoring. Currently, clinically common inflammation detection indexes mainly comprise white blood cell count, neutrophil proportion, serum markers such as C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6) and the like in blood convention. Although the indexes can provide certain inflammation information, the method still has obvious limitations that if a single index is often insufficient in specificity, infectious and non-infectious inflammations are difficult to distinguish, the dynamic changes of the indexes are lagged, the inflammation process or the treatment effect cannot be reflected in real time, and most markers can be raised in various inflammation states, so that the accurate judgment of the inflammation type and the immune state is not facilitated. Taking interferon-gamma (IFN-gamma) as an example, the concentration of the interferon-gamma can be remarkably increased in various inflammatory processes, and the interferon-gamma can be used as an important molecular marker for inflammatory activation. IFN-gamma is secreted mainly by activated T cells, NK cells, etc., amplifies inflammatory response through forward regulatory loops, and is markedly elevated in infectious inflammation (e.g., tuberculosis, influenza) and autoimmune diseases (e.g., rheumatoid arthritis). However, IFN-gamma detection still has the problems of complex operation, high cost, insignificant change in part of inflammation types and the like, and limits the clinical popularization and comprehensive application value of the IFN-gamma detection. Therefore, the ideal marker and the corresponding detection method which have strong specificity, high sensitivity and convenient detection and can reflect the inflammatory state more comprehensively are still lacking in the prior art. In view of this technical gap, the present invention proposes TKFC (Triokinase/FMN cyclase) as an inflammation marker for use in inflammation detection. Although the sequence of TKFC has been previously disclosed, its expression changes during inflammation and its use as a marker of inflammation have not been reported to date. Disclosure of Invention The present invention aims to solve at least one of the above technical problems in the prior art. To this end, the present invention aims to provide an inflammatory marker and its use. The invention reveals the application potential of TKFC in inflammation detection for the first time, finds TKFC expression condition on cell membranes based on immune cells, can accurately judge immune cell states and/or organism inflammation conditions, and provides a new technical means for accurate identification and monitoring of inflammation. In a first aspect of the invention there is provided the use of a triple kinase/FMN cyclase (TKFC) on the cell membrane of an immune cell as an immune cell surface marker for characterising the status of an immune cell and/or inflammatory conditions of the body. In some embodiments of the invention, the immune cell state comprises a resting state and an activated state. In some embodiments of the invention, the term "resting state" refers to a state in which a cell is not stimulated by a particular antigen, cytokine or danger signal, characterized by low metabolic activity, low proliferative capacity, functional resting, but has the ready state of rapid response potential. Resting cells are constantly circulating, recruiting, and monitoring microenvironment signals in vivo via their antigen receptors (e.g., TCR, BCR) and Pattern Recognition Receptors (PRRs), but do not respond to their normal tissues. In some embodiments of the invention, the term "activated state" refers to a state of functional performance in which an immune cell undergoes a series of intracellular signal transduction, metabolic reprogramming, gene expression remodeling upon receiving a specific antigen, cytokine, or danger signal stimulus, thereby achieving proliferative capacity and specific effector functions. In the present invention, the transition between "resting state" and "activated state" is the core of initiation, execution and termination of an immune response. This process is also a highly regulated