WO2019069449A1 - Procédé de mesure - Google Patents

Procédé de mesure Download PDF

Info

Publication number
WO2019069449A1
WO2019069449A1 PCT/JP2017/036462 JP2017036462W WO2019069449A1 WO 2019069449 A1 WO2019069449 A1 WO 2019069449A1 JP 2017036462 W JP2017036462 W JP 2017036462W WO 2019069449 A1 WO2019069449 A1 WO 2019069449A1
Authority
WO
WIPO (PCT)
Prior art keywords
cells
killer
factor
blood
threshold
Prior art date
Application number
PCT/JP2017/036462
Other languages
English (en)
Japanese (ja)
Inventor
純児 赤木
Original Assignee
純児 赤木
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 純児 赤木 filed Critical 純児 赤木
Priority to JP2018517354A priority Critical patent/JPWO2019069449A1/ja
Priority to PCT/JP2017/036462 priority patent/WO2019069449A1/fr
Publication of WO2019069449A1 publication Critical patent/WO2019069449A1/fr

Links

Images

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing

Definitions

  • the present invention relates to a method of measuring blood.
  • killer T cells exert an immune function.
  • the present invention provides a novel measuring method for killer T cells.
  • the blood measuring apparatus comprises the same killer T cell measuring step of measuring the first proportion of CD8 factor expressing CD8 factor and becoming killer T cells in T cells expressing CD8 factor in blood.
  • the measurement results are output according to a PD1 killer cell detection step of measuring a second proportion of killer T cells expressing CD8 factor and PD1 factor in T cells expressing CD8 factor.
  • the first percentage threshold is in the range of 30% to 60%.
  • the first percentage threshold is 46.4%.
  • the second percentage threshold is in the range of 2% to 12%.
  • the second percentage threshold is 6.76%.
  • the step of extracting only T cells that expressed CD8 factor from blood is included.
  • the blood measurement method of the present invention comprises the same steps in the same blood as the killer T cell measurement step of measuring the first proportion of CD8 factor expressing CD8 factor and becoming killer T cells in T cells expressing CD8 factor in blood. Measuring the second proportion of killer T cells expressing CD8 factor and expressing PD1 factor in T cells expressing CD8 factor, and an output step outputting the measurement result according to Have.
  • FIG. 2 is an explanatory view of the principle of the measuring device 1; It is explanatory drawing of the measuring method. It is explanatory drawing of the survival rate by the difference of a 1st ratio. It is explanatory drawing of the survival rate by the difference of a 2nd ratio. It is explanatory drawing represented to the above 4 quadrants.
  • Measurement results for Alzheimer's disease mice It is a measurement result with respect to the person whose immunity was aged. It is a measurement result for healthy adults. It is explanatory drawing of the result of having made the terminal cancer patient aspirate high concentration hydrogen gas (H2).
  • H2 high concentration hydrogen gas
  • FIG. 1 is an explanatory view of a measuring device 1 of the present invention.
  • the measuring apparatus 1 has a blood inlet 2 for taking in blood extracted from a human body (for example, a patient) into the apparatus, and an output unit for outputting various measurement and judgment results to the blood. It has three.
  • FIG. 2 is an explanatory view of the principle of the measuring device 1.
  • the blood contains dendritic cells such as (1).
  • These (1) dendritic cells are partially transformed into T cells such as (2) by various stimuli, commands, time lapses, and the like.
  • T cells such as (2) are killer T cells (hereinafter referred to as "CD8 + Killer T cells") that express CD8 factor such as (3) by various stimuli, commands, time course, etc. Change.
  • various stimuli at this time are the invasion of pathogenic bacteria and viruses and the occurrence of cancer.
  • the CD8 + Killer T cells such as (3) have an effect of attacking pathogens / viruses and cancer cells. As a result, it has been speculated that if the proportion of CD8 + Killer T cells is high, it can be said that large immunity is working.
  • FIG. 3 is an explanatory view of a measuring method.
  • the blood contains dendritic cells, T cells, CD8 + Killer T cells, PD-1-Killer-T cells, and many other cells.
  • the blood is carried into the blood inlet 2 of the measuring device 1 of FIG. Thereafter, only T cells, CD8 + Killer T cells, and PD-1-Killer-T cells are sorted by the method of pack scan. Then, the number of T cells, CD8 + Killer T cells, PD-1-Killer-T cells is measured.
  • the ratio of the number of CD8 + Killer T cells (hereinafter, the first ratio) is measured and calculated from the total number of T cells, CD8 + Killer T cells and PD-1-Killer-T cells.
  • the ratio (hereinafter, the second ratio) of the number of PD-1-Killer-T cells is measured and calculated.
  • FIG. 4 is an explanatory view of the survival rate according to the first ratio difference.
  • Blood was extracted from multiple terminal cancer patients and the first percentage was measured. Assuming that the threshold of the first ratio is 46.4%, the survival period with the patient group exceeding the threshold (first threshold) is a line of KillerTcells> 46.4%. On the other hand, assuming that the threshold of the first ratio is 46.4%, the survival time with the patient group below that threshold (first threshold) is a line of KillerTcells ⁇ 46.4%. It can be seen that the survival rates are quite different. Specifically, in the line of KillerTcells> 46.4%, it can be seen that the survival rate falls to about 75% after about 20 days, but is stable thereafter. On the other hand, in the line of KillerTcells ⁇ 46.4%, it can be seen that the survival rate drops to about 10% about 22 days ago.
  • the first threshold is set to 46.4%.
  • the reason was adopted as the optimum value because the sensitivity and specificity were high.
  • the first threshold is 46.4%, but it is currently judged that it can be judged appropriately to some extent if it is in the range of 40% to 50% even if the first threshold is changed. .
  • FIG. 5 is an explanatory view of the survival rate according to the second ratio difference.
  • the second rate threshold is 6.76%
  • the survival time of the patient group exceeding the threshold (second threshold) is a line of PD-1 (+) Killer Tcells> 6.76%.
  • the threshold of the second ratio is 6.76%
  • the survival time of the patient group below that threshold (second threshold) is a line of PD-1 (+) Killer Tcells ⁇ 6.76%. It can be seen that the survival rates are quite different. Specifically, in the line of PD-1 (+) Killer Tcells ⁇ 6.76%, the survival rate falls to about 92% after about 10 days, but it is understood that the survival rate is stable thereafter. On the other hand, in the PD-1 (+) Killer Tcells> 6.76 %% line, it can be seen that the survival rate drops to about 0% about 37 days ago.
  • the second threshold is set to 6.76%.
  • the reason was adopted as the optimum value because the sensitivity and specificity were high.
  • the second threshold was set to 6.76%, but it is currently judged that it can be judged appropriately to some extent as long as the second threshold is changed within the range of 4.5% to 10%. ing.
  • PD-1 (+) Killer Tcells is one in which the function of Killer T cells is suppressed because PD1 factor is expressed by a substance produced by cancer cells and the like among such Killer T cells. This PD1 factor is expressed when mitochondrial function in killer T cells is reduced. We believe that this is the cause that killer T cells can not exert their original power.
  • KillerTcells Conventionally, the ratio between KillerTcells and PD-1 (+) KillerTcells has been studied independently. Or, KillerTcells simply thought that there should be only a large number, PD-1 (+) KillerTcells simply thought that there should be a small number. However, the inventor has found that the two indices should be considered in four quadrants, not separately and independently. And I think that the treatment plan etc. should be decided depending on which quadrant it is in.
  • FIG. 6 is an explanatory view represented in the above four quadrants.
  • a quadrant whose Killer T cells exceeds the first threshold and whose PD-1 (+) Killer T cells is less than the second threshold is called category 1 (Cat 1).
  • the quadrant in which the Killer T cells exceed the first threshold and the PD-1 (+) Killer T cells exceeds the second threshold is referred to as category 2 (Cat 2).
  • a quadrant in which KillerTcells is less than a first threshold and PD-1 (+) KillerTcells is less than a second threshold is referred to as category 3 (Cat 3).
  • a quadrant in which Killer T cells is less than the first threshold and PD-1 (+) Killer T cells is greater than the second threshold is referred to as category 4 (Cat 4).
  • This category classification is the method of the present invention.
  • FIG. 7 shows the measurement results for Alzheimer's disease mice.
  • FIG. 8 shows the results of measurement for a person who has developed an immune system.
  • FIG. 9 shows the measurement results for healthy adults.
  • FIG. 10 is an explanatory view of the result of allowing a terminal cancer patient to aspirate high concentration hydrogen gas (H 2).

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Immunology (AREA)
  • Urology & Nephrology (AREA)
  • Cell Biology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

Le problème décrit par la présente invention est de fournir un dispositif de mesure et un procédé de mesure qui fonctionnent selon un nouveau point de vue par rapport aux lymphocytes T tueurs. La solution selon l'invention concerne un dispositif de mesure s'exerçant sur le sang qui émet un résultat de mesure en fonction : d'une étape de mesure de lymphocytes T tueurs consistant à mesurer une première proportion, correspondant à la proportion de lymphocytes T qui expriment des facteurs CD8 et qui constituent des lymphocytes T tueurs parmi des lymphocytes T exprimant des facteurs CD8 dans le sang ; et d'une étape de détection de cellules tueuses PD1 consistant à mesurer une seconde proportion, correspondant à la proportion de lymphocytes T tueurs qui expriment des facteurs CD8 et qui expriment également des facteurs PD1 parmi les mêmes lymphocytes T exprimant des facteurs CD8 dans le sang.
PCT/JP2017/036462 2017-10-06 2017-10-06 Procédé de mesure WO2019069449A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2018517354A JPWO2019069449A1 (ja) 2017-10-06 2017-10-06 測定方法
PCT/JP2017/036462 WO2019069449A1 (fr) 2017-10-06 2017-10-06 Procédé de mesure

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/JP2017/036462 WO2019069449A1 (fr) 2017-10-06 2017-10-06 Procédé de mesure

Publications (1)

Publication Number Publication Date
WO2019069449A1 true WO2019069449A1 (fr) 2019-04-11

Family

ID=65994446

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2017/036462 WO2019069449A1 (fr) 2017-10-06 2017-10-06 Procédé de mesure

Country Status (2)

Country Link
JP (1) JPWO2019069449A1 (fr)
WO (1) WO2019069449A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2014214093A (ja) * 2013-04-23 2014-11-17 国立大学法人岡山大学 免疫疲弊ｃｄ８＋ｔ細胞の機能改善薬、がん治療薬及びメタボリック症候群の予防または治療薬
JP2017165752A (ja) * 2014-08-19 2017-09-21 国立大学法人 岡山大学 ビグアニド系抗糖尿病薬と免疫抑制因子解除剤又は共刺激受容体作動薬との併用による免疫能異常に伴う疾患の治療及び／又は予防

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2014214093A (ja) * 2013-04-23 2014-11-17 国立大学法人岡山大学 免疫疲弊ｃｄ８＋ｔ細胞の機能改善薬、がん治療薬及びメタボリック症候群の予防または治療薬
JP2017165752A (ja) * 2014-08-19 2017-09-21 国立大学法人 岡山大学 ビグアニド系抗糖尿病薬と免疫抑制因子解除剤又は共刺激受容体作動薬との併用による免疫能異常に伴う疾患の治療及び／又は予防

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHEN DS: "Oncolpgy Meets Immunology: The Cancer-Immunity Cycle", IMMUNITY, vol. 39, no. 1, 25 July 2013 (2013-07-25), pages 1 - 10, XP002742399, DOI: doi:10.1016/j.immuni.2013.07.012 *
NISHIDA, MIKAKO ET AL: "T Cells for Tumor Immunity: Exhaustion and Metabolic Control Therefor. Experimental Medicine. Part I Fundamentals of Tumor Immune Responsiveness and Control Mechanism Therefor. Chapter 1 Immune Cells and Immune Molecules for Tumor Immunity", vol. 34, no. 12, 2016, pages 24 - 29 *

Also Published As

Publication number Publication date
JPWO2019069449A1 (ja) 2019-11-14

Similar Documents

Publication Publication Date Title
Rossoni et al. Comparison of the hemolytic activity between C. albicans and non-albicans Candida species
Li et al. A pilot study of mothers and infants reveals fetal sex differences in the placental transfer efficiency of heavy metals
Sakamoto et al. Implications of mercury concentrations in umbilical cord tissue in relation to maternal hair segments as biomarkers for prenatal exposure to methylmercury
Xiang et al. Analysis of children's serum fluoride levels in relation to intelligence scores in a high and low fluoride water village in China
Saxena et al. Role of mean platelet volume (MPV) in diagnosis of acute appendicitis
Kaur Association between ABO blood group and hypertension among post-menopausal females of North India
WO2019069449A1 (fr) Procédé de mesure
Liu et al. Cytogenetic analysis in 16-year follow-up study of a mother and fetus exposed in a radiation accident in Xinzhou, China
Arbon et al. Eosinophil count, allergies, and rejection in pediatric heart transplant recipients
Shokry et al. Oxidant-antioxidant balance in childhood asthma
Kan et al. Geohelminth infection of children from rural plantations and urban slums in Malaysia
Rao Scrofuloderma associated with tuberculosis verrucosa cutis
Maggi Special issue nutrition and musculoskeletal health
Sahoo et al. A Discussion on Second Wave of COVID-19 Pandemic in India
Marlentine et al. The relationship between ABO blood group typing with tinea corporis and or tinea cruris in Tanjung Gusta Prison, Medan-Indonesia
Rajekar et al. ISSN-O: 2458-868X, ISSN–P: 2458-8687
Wang et al. Trend of the coronavirus disease-2019 epidemic in China after the lockdown of Wuhan City on January 23, 2020
Keita et al. Mutations in spike gene of SARS-CoV-2 that are associated with a higher viral load: a clinical case study
Mahdi et al. Prevalence of Cutaneous Warts Caused by Human Papillomaviruses and the Effect of Vitamin D with it's Distribution Among Patients in Thi-Qar Province
Chunhong et al. Human brucellosis epidemiological characteristics in Qiqihar, Heilongjiang, 2004–2019
Nadeem et al. LOWER MATERNAL VITAMIN-D LEVELS'ASSOCIATION WITH EARLY-ONSET NEONATAL SEPSIS IN TERM NEONATES: Lower Maternal Vitamin-D Levels with Early-Onset Neonatal Sepsis
Rencani et al. The relationship of various risk factors to the incidence of Herpes Zoster at PKU Muhammadiyah Gamping Hospital
Hildebrand et al. Posttraumatic immune response and its modulation
Quanyong et al. A12048 The effects of nitrendipine/atenolol combination tablets on the blood lipid level in the patients with mild-to-moderate essential hypertension---A prospective study of single treatment group
Guo et al. Arsenic induces Th1/Th2 imbalance in immune and non-immune organs

Legal Events

Date Code Title Description
ENP Entry into the national phase

Ref document number: 2018517354

Country of ref document: JP

Kind code of ref document: A

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 17927905

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 17927905

Country of ref document: EP

Kind code of ref document: A1