WO2021107551A1 - Biomarqueur pour distinguer des maladies infectieuses provoquées par des mycobactéries non tuberculeuses - Google Patents

Biomarqueur pour distinguer des maladies infectieuses provoquées par des mycobactéries non tuberculeuses Download PDF

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WO2021107551A1
WO2021107551A1 PCT/KR2020/016665 KR2020016665W WO2021107551A1 WO 2021107551 A1 WO2021107551 A1 WO 2021107551A1 KR 2020016665 W KR2020016665 W KR 2020016665W WO 2021107551 A1 WO2021107551 A1 WO 2021107551A1
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mycobacterium
tuberculous
infectious diseases
disease
group
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Korean (ko)
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신성재
박지해
김크은산
고원중
전병우
김수영
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주식회사 큐라티스
연세대학교 산학협력단
사회복지법인 삼성생명공익재단
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Publication of WO2021107551A1 publication Critical patent/WO2021107551A1/fr

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    • 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
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N24/00—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects
    • G01N24/08—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects by using nuclear magnetic resonance
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/62—Detectors specially adapted therefor
    • G01N30/72—Mass spectrometers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
    • 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
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
    • G01N33/6848—Methods of protein analysis involving mass spectrometry
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
    • G01N2030/8809—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample
    • G01N2030/8813—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample biological materials
    • G01N2030/8818—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample biological materials involving amino acids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/26—Infectious diseases, e.g. generalised sepsis

Definitions

  • the present invention relates to a biomarker for discriminating an infectious disease caused by non-tuberculous mycobacteria, and a kit or a discrimination method for the discrimination.
  • Mycobacterium includes not only species that cause serious diseases in humans and animals, such as tuberculosis, tuberculosis bovine tuberculosis, and leprosy, but also fungal species called opportunistic bacteria, and parasitic objects found in the natural environment. About 72 species such as saprophytic species are known so far, of which 25 are known to be related to human diseases. These Mycobacterium genus are not easily dyed with commonly used dyeing solutions, but once dyed, they are also called acid-fighting bacteria because they are not easily decolorized even when treated with alcohol or hydrochloric acid.
  • Nontuberculous mycobacteria refers to mycobacteria other than Mycobacterium tuberculosis complex and Mycobacterium leprae.
  • MAC Mycobacterium avium complex
  • MAB Mycobacterium abscessus
  • M. abscessus subspecies Absesu. s M. abscessus subspecies abscessus
  • M. abscessus subspecies massiliense M. abscessus subspecies massiliense
  • One object of the present invention is to provide a biomarker composition for distinguishing infectious diseases caused by non-tuberculous mycobacteria.
  • Another object of the present invention is to provide a kit for distinguishing infectious diseases caused by non-tuberculous mycobacteria.
  • Another object of the present invention is to provide a method for distinguishing infectious diseases caused by non-tuberculous mycobacteria.
  • biomarker composition for differential diagnosis of infectious diseases caused by non-tuberculous mycobacteria, including metabolites.
  • the biomarker for differential diagnosis according to the present invention is a substance that can distinguish and diagnose infectious diseases that have occurred after infection with non-tuberculous mycobacteria, and increases in biological samples derived from subjects that develop for each disease after infection with non-tuberculous mycobacteria. or a metabolite showing a decreasing pattern, preferably a blood metabolite.
  • the "metabolite” is also called a metabolite or metabolite, and is an intermediate product or product of metabolism.
  • metabolites are fuel, structure, signaling, catalytic and inhibitory effects on enzymes, their own catalytic activity (usually as cofactors for enzymes), defense, and interactions with other organisms (eg, pigments, aromatic compounds). , pheromones).
  • Primary metabolites are directly involved in normal growth, development and reproduction. Secondary metabolites are not directly involved in these processes, but usually have important ecological functions.
  • the metabolite refers to a sample of biological origin, that is, a metabolite obtained from a biological sample
  • the biological sample refers to a biological body fluid, tissue or cell, for example, whole blood, leukocyte. (leukocytes), peripheral blood mononuclear cells, buffy coat, plasma, serum, sputum, tears, mucus, nasal washes, nasal aspirate, breath, urine, semen, saliva, peritoneal washings, ascites, cystic fluid , meningeal fluid, amniotic fluid, glandular fluid, pancreatic fluid, lymph fluid, pleural fluid, nipple aspirate, bronchial aspirate ( One selected from the group consisting of bronchial aspirate, synovial fluid, joint aspirate, organ secretions, cell, cell extract, and cerebrospinal fluid. It may be more than, but preferably whole blood (whole blood), plasma (plasma) or serum (serum) may be, and more of bronchial
  • whole blood, plasma or serum may be pretreated to detect the metabolite.
  • it may include filtration, distillation, extraction, separation, concentration, inactivation of interfering components, addition of reagents, and the like.
  • the metabolite may include a substance produced by metabolism and metabolic processes or a substance generated by chemical metabolism by biological enzymes and molecules.
  • the metabolite is preferably a metabolite obtained from a liquid sample derived from blood, preferably serum, and specific examples include amino acids, amino acid derivatives, allantoin, malic acid. ) and glycerol 3-phosphate (Glycerol 3-phosphate) may include at least one selected from the group consisting of.
  • the malic acid is preferably in the L-form, but is not limited thereto.
  • the amino acid and its derivatives may include one or more selected from the group consisting of tyrosine, isoleucine, citrulline, tryptophan, and methionine.
  • the amino acid may be in the L-form (L-form), preferably tyrosine, isoleucine, tryptophan or methionine is L-form It is preferred, but not limited thereto.
  • the non-tuberculous mycobacteria are Mycobacterium avium (M. avium), Mycobacterium abscessus (M. abscessus), Mycobacterium flavesense (M. flavescence), Mycobacterium Rum africanum (M. africanum), Mycobacterium bovis (M. bovis), Mycobacterium cellone (M. chelonae), Mycobacterium cellatum (M. celatum), Mycobacterium portuitum (M. fortuitum), Mycobacterium gordonae (M. gordonae), Mycobacterium gastri (M. gastri), Mycobacterium haemophilum (M.
  • Mycobacterium intracellulare M. intracellulare
  • mycobacterium kansasii M. kansasii
  • mycobacterium malmoens M. malmoense
  • mycobacterium marinum M. marinum
  • mycobacterium sulgai M) szulgai
  • Mycobacterium terrae M. terrae
  • Mycobacterium scrofulaceum M. scrofulaceum
  • Mycobacterium Ulcerans M. ulcerans
  • Mycobacterium simiae M. simiae
  • Mycobacterium xenopi M. xenopi
  • M. xenopi is preferably selected from the group consisting of, but is not limited thereto.
  • the non-tuberculous mycobacterium-infectious disease includes all clinical symptoms caused by the non-tuberculous mycobacterium infection, and the infectious disease is a lung disease, lymphadenitis, skin/soft tissue/bone infection or disseminated disease, etc. may include.
  • the infectious lung disease caused by the non-tuberculous mycobacterium may be of an upper lobe cavitary form, a nodular bronchiectatic form, or a combination thereof.
  • the infectious lung disease may be accompanied by cough, sputum, blood sputum, fever, dyspnea, chest pain, or a combination thereof.
  • the biomarker composition of the present invention distinguishes whether the disease or possible disease developed in the subject after infection by non-tuberculous mycobacteria is upper lobe cavitary form lung disease or nodular bronchiectatic form lung disease. Diagnosis is possible.
  • the present invention relates to a kit for differential diagnosis of non-tuberculous mycobacterium infectious diseases, including a quantitative device for measuring the concentration of metabolites.
  • the metabolite refers to a sample of biological origin, that is, a metabolite obtained from a biological sample
  • the biological sample refers to a biological body fluid, tissue or cell, for example, whole blood, leukocyte. (leukocytes), peripheral blood mononuclear cells, buffy coat, plasma, serum, sputum, tears, mucus, nasal washes, nasal aspirate, breath, urine, semen, saliva, peritoneal washings, ascites, cystic fluid , meningeal fluid, amniotic fluid, glandular fluid, pancreatic fluid, lymph fluid, pleural fluid, nipple aspirate, bronchial aspirate ( One selected from the group consisting of bronchial aspirate, synovial fluid, joint aspirate, organ secretions, cell, cell extract, and cerebrospinal fluid. It may be more than, but preferably whole blood (whole blood), plasma (plasma) or serum (serum) may be, and more of bronchial
  • whole blood, plasma or serum may be pretreated to detect the metabolite.
  • it may include filtration, distillation, extraction, separation, concentration, inactivation of interfering components, addition of reagents, and the like.
  • the metabolite is preferably a metabolite obtained from a liquid sample derived from blood, preferably serum, and specific examples include amino acids, amino acid derivatives, allantoin, malic acid. ) and glycerol 3-phosphate (Glycerol 3-phosphate) may include at least one selected from the group consisting of.
  • the malic acid is preferably in the L-form, but is not limited thereto.
  • the amino acid and its derivatives may include one or more selected from the group consisting of tyrosine, isoleucine, citrulline, tryptophan, and methionine.
  • the amino acid may be in the L-form (L-form), preferably tyrosine, isoleucine, tryptophan or methionine is L-form It is preferred, but not limited thereto.
  • the quantitative device may be a nuclear magnetic resonance spectrometer (NMR), chromatography, or mass spectrometer, but is not limited thereto.
  • NMR nuclear magnetic resonance spectrometer
  • chromatography chromatography
  • mass spectrometer but is not limited thereto.
  • Chromatography used in the present invention is high performance liquid chromatography (HPLC), liquid-solid chromatography (Liquid-Solid Chromatography, LSC), paper chromatography (Paper Chromatography, PC), thin layer chromatography (Thin) -Layer Chromatography (TLC), Gas-Solid Chromatography (GSC), Liquid-Liquid Chromatography (LLC), Foam Chromatography (FC), Emulsion Chromatography (Emulsion) Chromatography (EC), Gas-Liquid Chromatography (GLC), Ion Chromatography (IC), Gel Filtration Chromatography (GFC) or Gel Permeation Chromatography (Gel Permeation Chromatography, GPC), but is not limited thereto, and any quantitative chromatography commonly used in the art may be used.
  • HPLC high performance liquid chromatography
  • LSC liquid-solid chromatography
  • PC Paper chromatography
  • TLC thin layer chromatography
  • GSC Gas-Solid Chromatography
  • LLC Liquid
  • the mass spectrometer may use a conventionally known mass spectrometer without any particular limitation, but specifically, for example, a Fourier transform mass spectrometer (FTMS), a Malditope mass spectrometer (MALDI-TOF MS), It may be Q-TOF MS or LTQ-Orbitrap MS, but is not limited thereto.
  • FTMS Fourier transform mass spectrometer
  • MALDI-TOF MS Malditope mass spectrometer
  • Q-TOF MS Q-TOF MS or LTQ-Orbitrap MS, but is not limited thereto.
  • the biomarker composition of the present invention distinguishes whether the disease or possible disease occurring in the subject after infection by non-tuberculous mycobacteria is upper lobe cavitary form lung disease or nodular bronchiectatic form lung disease This is possible.
  • the definition of non-tuberculous mycobacterium and its infectious disease overlaps with those described in the biomarker composition of the present invention, and the description thereof will be omitted below to avoid excessive congestion of the specification.
  • it relates to a method for providing information for distinguishing infectious diseases of non-tuberculous mycobacteria, comprising measuring the expression level of a metabolite in a biological sample isolated from a target subject.
  • the "target individual” means an individual with a high probability of infection as an individual whose infection by non-tuberculous mycobacterium is uncertain, or has been infected or diagnosed as infected by non-tuberculous mycobacterium, but the type of infectious disease is uncertain means an object.
  • the "biological sample” refers to any material, biological fluid, tissue or cell obtained from or derived from an individual, and includes whole blood, leukocytes, and peripheral blood mononuclear cells.
  • a step of pre-treating the biological sample preferably whole blood, plasma or serum may be performed prior to measuring the expression level of the metabolite.
  • the pretreatment may include, for example, filtration, distillation, extraction, separation, concentration, inactivation of interfering components, addition of reagents, and the like, but is not limited thereto.
  • the metabolite is preferably a metabolite obtained from a liquid sample derived from blood, preferably serum, amino acid, amino acid derivative, allantoin, malic acid, and glycerol 3- It may include one or more selected from the group consisting of phosphate (Glycerol 3-phosphate).
  • the malic acid is preferably in the L-form, but is not limited thereto.
  • the amino acid and its derivatives may include one or more selected from the group consisting of tyrosine, isoleucine, citrulline, tryptophan, and methionine.
  • the amino acid may be in the L-form (L-form), preferably tyrosine, isoleucine, tryptophan or methionine is L-form It is preferred, but not limited thereto.
  • the quantitative device may be a nuclear magnetic resonance spectrometer (NMR), chromatography, or mass spectrometer, but is not limited thereto.
  • NMR nuclear magnetic resonance spectrometer
  • chromatography chromatography
  • mass spectrometer but is not limited thereto.
  • the expression level of the metabolite may be performed using a quantitative device.
  • the quantitative device may be a nuclear magnetic resonance spectrometer (NMR), chromatography, or mass spectrometer, but is not limited thereto.
  • Chromatography used in the present invention is high performance liquid chromatography (HPLC), liquid-solid chromatography (Liquid-Solid Chromatography, LSC), paper chromatography (Paper Chromatography, PC), thin layer chromatography (Thin) -Layer Chromatography (TLC), Gas-Solid Chromatography (GSC), Liquid-Liquid Chromatography (LLC), Foam Chromatography (FC), Emulsion Chromatography (Emulsion) Chromatography (EC), Gas-Liquid Chromatography (GLC), Ion Chromatography (IC), Gel Filtration Chromatography (GFC) or Gel Permeation Chromatography (Gel Permeation Chromatography, GPC), but is not limited thereto, and any quantitative chromatography commonly used in the art may be used.
  • HPLC high performance liquid chromatography
  • LSC liquid-solid chromatography
  • PC Paper chromatography
  • TLC thin layer chromatography
  • GSC Gas-Solid Chromatography
  • LLC Liquid
  • the mass spectrometer may use a conventionally known mass spectrometer without any particular limitation, but specifically, for example, a Fourier transform mass spectrometer (FTMS), a Malditope mass spectrometer (MALDI-TOF MS), It may be Q-TOF MS or LTQ-Orbitrap MS, but is not limited thereto.
  • FTMS Fourier transform mass spectrometer
  • MALDI-TOF MS Malditope mass spectrometer
  • Q-TOF MS Q-TOF MS or LTQ-Orbitrap MS, but is not limited thereto.
  • the disease that can develop or develop in the target individual is nodular bronchiectatic form lung It may further include the step of predicting that the disease is.
  • the disease that can develop or develop in the target individual is upper lobe cavitary form It may further include the step of predicting to be a lung disease.
  • glycerol 3-phosphate malic acid
  • isoleucine citrulline
  • tryptophan Glycerol 3-phosphate
  • malic acid When the expression level of one or more selected from the group consisting of Tryptophan) and methionine is increased compared to the control group, the disease occurring or possible in the target subject is a nodular bronchiectatic form lung disease. It may include further steps.
  • control is a normal control that is not infected with non-tuberculous mycobacteria
  • the median value of the patient population (or the average value of the patients) infected with non-tuberculous mycobacteria, or the upper lobe cavitation after infection with non-tuberculous mycobacteria (upper lobe cavitary form) may be the median value (or the average value of the corresponding patients) of the patient population who developed lung disease.
  • the method may further include predicting that the disease that can be developed is a nodular bronchiectatic form lung disease.
  • control is a normal control not infected with non-tuberculous mycobacteria
  • the median value of the patient population (or the average value of the patients) infected with non-tuberculous mycobacteria, or the upper lobe cavitation after infection with non-tuberculous mycobacteria (upper lobe cavitary form) may be the median value (or the average value of the patient) of the patient population who developed lung disease.
  • glycerol 3-phosphate, malic acid, isoleucine, citrulline, tryptophan measured with respect to the biological sample of the subject of the present invention in the present invention.
  • the expression level of one or more selected from the group consisting of (Tryptophan) and methionine is reduced compared to the control group, the disease occurring or possible in the target subject is an upper lobe cavitary form lung disease. It may further include the step of predicting.
  • control group is a normal control that is not infected with non-tuberculous mycobacteria
  • the median value of the patient population (or the average value of the patients) infected with non-tuberculous mycobacteria, or bronchiectasis after infection with non-tuberculous mycobacteria ( nodular bronchiectatic form) may be the median (or mean value of those patients) of a patient population with onset of lung disease.
  • the method may further include predicting that the onset or possible disease is an upper lobe cavitary form lung disease.
  • control group is a normal control that is not infected with non-tuberculous mycobacteria
  • the median value of the patient population (or the average value of the patients) infected with non-tuberculous mycobacteria, or bronchiectasis after infection with non-tuberculous mycobacteria ( nodular bronchiectatic form) may be the median (or mean value of those patients) of a patient population with onset of lung disease.
  • a disease that has occurred or is highly likely to occur in a target subject by non-tuberculous mycobacteria is a nodular bronchiectatic form lung disease or upper lobe cavitary form lung disease. If predicted, it may further include the step of performing appropriate treatment, such as administration of a drug for the disease, for example, antibiotics to the target subject.
  • the "antibiotic” may be rifampin, isoniazid, ethambutol, pyrazinamide (PZA), quinolone, or aminoglycoside, but is not limited thereto.
  • the quinolone antibiotic is nalidixic acid, marbofloxacin, oxolinic acid, moxifloxacin, trovafloxacin, gatifloxacin, Flumequine, prulifloxacin, gemifloxacin, ciprofloxacin, sitafloxacin, or clinafloxacin, etc., but may not be limited thereto.
  • aminoglycoside antibiotics include streptomycin, neomycin, framycetin, gentamycin, novobiocin, kanamycin, and amica. It may be syn (amikacin), sisomycin (sisomycin) or spectinomycin (spectinomycin), but is not limited thereto.
  • the type of infectious disease caused by non-tuberculous mycobacteria can be predicted, and the course, prognosis, or therapeutic effect of the disease can also be tracked.
  • non-tuberculous mycobacterium and its infectious disease overlaps with that described in the biomarker composition of the present invention, and thus description thereof will be omitted below to avoid excessive congestion of the specification.
  • the present invention by measuring the expression level of blood metabolites in a biological sample of a target individual, it is possible to simply, easily and accurately classify and diagnose the types of diseases that develop or are likely to develop after infection by non-tuberculous mycobacteria.
  • MAC Mycobacterium avium complex
  • Figure 2 is in an embodiment of the present invention L from serum samples of patients with mycobacterium avium complex (MAC)-infected lung disease patients with nodular bronchiectatic form and upper lobe cavitary form; - It shows a graph comparing the expression level of L-Malic acid.
  • MAC mycobacterium avium complex
  • MAC Mycobacterium avium complex
  • MAC 7 is a mycobacterium avium complex (MAC) in an embodiment of the present invention in a patient with a successful treatment among patients with a lung disease, a patient with nodular bronchiectatic form and an upper lobe cavitary form ) shows a graph comparing the expression level of glycerol 3-phosphate in a patient's serum sample.
  • MAC mycobacterium avium complex
  • MAC mycobacterium avium complex
  • MAC 9 is a mycobacterium avium complex (MAC) in a patient with a failed treatment among patients with a lung disease in an embodiment of the present invention, a patient with nodular bronchiectatic form and an upper lobe cavitary form ) shows a graph comparing the expression level of L-tryptophan in a patient's serum sample.
  • MAC mycobacterium avium complex
  • MAC 10 is a mycobacterium avium complex (MAC) in an unsuccessful treatment among patients with a lung disease infection in an embodiment of the present invention, a patient with nodular bronchiectatic form and an upper lobe cavitary form ) shows a graph comparing the expression level of citrulline in a patient's serum sample.
  • MAC mycobacterium avium complex
  • MAC mycobacterium avium complex
  • MAC 12 is a mycobacterium avium complex (MAC) in an unsuccessful treatment among patients with lung disease in an embodiment of the present invention, a patient with nodular bronchiectatic form and an upper lobe cavitary form ) shows a graph comparing the expression level of L-methionine in a patient's serum sample.
  • MAC mycobacterium avium complex
  • MAC 13 is a mycobacterium avium complex (MAC) in an unsuccessful patient among patients with infectious lung disease in an embodiment of the present invention, a patient with nodular bronchiectatic form and an upper lobe cavitary form ) shows a graph comparing the expression level of L-isoleucine in a patient's serum sample.
  • MAC mycobacterium avium complex
  • the present invention relates to a method for providing information for distinguishing infectious diseases of non-tuberculous mycobacteria, comprising measuring the expression level of a metabolite in a biological sample isolated from a target subject.
  • the metabolite is preferably a metabolite obtained from a liquid sample derived from blood, preferably serum, amino acid, amino acid derivative, allantoin, malic acid, and glycerol 3- It may include one or more selected from the group consisting of phosphate (Glycerol 3-phosphate).
  • the amino acid and its derivatives may include one or more selected from the group consisting of tyrosine, isoleucine, citrulline, tryptophan, and methionine.
  • the malic acid and the amino acid may be in the L-form (L-form).
  • Serum samples from patients with Mycobacterium avium complex (74 patients in total) infected with the Mycobacterium avium complex collected at Samsung Hospital in Seoul for approximately 6 years from January 2012 to August 2016 were analyzed for the type of lung disease. Accordingly, serum samples from 44 patients with nodular bronchiectatic form and serum samples from 30 patients with upper lobe cavitary form were prepared. In addition, serum samples from 44 patients with nodular bronchiectatic form were prepared separately from 32 patients who succeeded in treatment and 12 patients who failed treatment, and from 30 patients with upper lobe cavitary form. Serum samples were also prepared separately from 14 patients who succeeded in treatment and 16 patients who failed treatment.
  • sample quality control SQC
  • SQC sample quality control
  • NB indicates the expression level of each metabolite in the serum samples of 44 patients with nodular bronchiectatic form lung disease, and UC is a patient with upper lobe cavitary form lung disease. Expression levels of each metabolite in 30 serum samples are shown.
  • NB represents the expression level of each metabolite in serum samples from 32 patients with nodular bronchiectatic form lung disease
  • UC represents the expression level of each metabolite in 14 patients with upper lobe cavitary form lung disease. Expression levels of each metabolite in serum samples are shown.
  • glycerol-3-phosphate in the blood metabolites is in the upper lobe cavitary form compared to patients with lung disease in nodular bronchiectatic form.
  • the expression was significantly increased in patients with lung disease.
  • the expression of L-Tyrosine was significantly reduced in patients with nodular bronchiectatic form lung disease compared to patients with upper lobe cavitary form lung disease.
  • NB indicates the expression level of each metabolite in serum samples of 12 patients with nodular bronchiectatic form lung disease
  • UC indicates the expression level of each metabolite in 16 patients with upper lobe cavitary form lung disease. Expression levels of each metabolite in serum samples are shown.
  • metabolites L-Tyrosine, L-Isoleucine, Citrulline, L-Tryptophan, L-Methionine, Allantoin , L-Malic acid and glycerol 3-phosphate can be used as biomarkers for distinguishing and diagnosing types of infectious diseases caused by non-tuberculous mycobacteria that have or are likely to develop in a subject. was found to be
  • the present invention relates to a biomarker for discriminating an infectious disease caused by non-tuberculous mycobacteria, and a kit or a discrimination method for the discrimination.

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Abstract

La présente invention concerne un biomarqueur pour distinguer et diagnostiquer différents types de maladies infectieuses provoquées par des mycobactéries non tuberculeuses et se produisant chez un sujet ; un kit pour la distinction et le diagnostic ; et un procédé pour la distinction et le diagnostic.
PCT/KR2020/016665 2019-11-25 2020-11-24 Biomarqueur pour distinguer des maladies infectieuses provoquées par des mycobactéries non tuberculeuses WO2021107551A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20130095454A (ko) * 2012-02-20 2013-08-28 엠앤디 (주) 결핵균 및 비결핵 항산균의 구별방법 및 조성물
KR101748296B1 (ko) * 2014-09-04 2017-06-19 연세대학교 산학협력단 마이코박테리움 압세수스 복합체 감염 폐질환 진단용 바이오마커 조성물
KR20180023393A (ko) * 2016-08-25 2018-03-07 솔젠트 (주) 결핵균 및 비결핵균 동시 검출용 진단키트

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20130095454A (ko) * 2012-02-20 2013-08-28 엠앤디 (주) 결핵균 및 비결핵 항산균의 구별방법 및 조성물
KR101748296B1 (ko) * 2014-09-04 2017-06-19 연세대학교 산학협력단 마이코박테리움 압세수스 복합체 감염 폐질환 진단용 바이오마커 조성물
KR20180023393A (ko) * 2016-08-25 2018-03-07 솔젠트 (주) 결핵균 및 비결핵균 동시 검출용 진단키트

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DE BUCK JEROEN, SHAYKHUTDINOV RUSTEM, BARKEMA HERMAN W., VOGEL HANS J.: "Metabolomic Profiling in Cattle Experimentally Infected with Mycobacterium avium subsp. paratuberculosis", PLOS ONE, vol. 9, no. 11, 5 November 2014 (2014-11-05), pages 1 - 11, XP055815032, DOI: 10.1371/journal.pone.0111872 *
KWON YONG-SOO: "Diagnosis and treatment of nontuberculous mycobacterial lung disease", JOURNAL OF KOREAN MEDICAL MEDICINE, vol. 31, no. 5, 1 January 2016 (2016-01-01), pages 649 - 659, XP055817513, ISSN: 1011-8934, DOI: 10.3346/jkms.2016.31.5.649 *

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