KR20230171298A - Information providing method for diagnosing non-tuberculous mycobacteria infection, and diagnostic kit using the same - Google Patents
Information providing method for diagnosing non-tuberculous mycobacteria infection, and diagnostic kit using the same Download PDFInfo
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- tuberculous
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- 238000000034 method Methods 0.000 title claims abstract description 11
- 208000015181 infectious disease Diseases 0.000 title abstract description 10
- 238000009007 Diagnostic Kit Methods 0.000 title abstract description 6
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000004472 Lysine Substances 0.000 claims abstract description 14
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 14
- DZQLQEYLEYWJIB-UHFFFAOYSA-N 4-aminobutanal Chemical compound NCCCC=O DZQLQEYLEYWJIB-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000004475 Arginine Substances 0.000 claims abstract description 11
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims abstract description 11
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims abstract description 11
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims abstract description 11
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims abstract description 11
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims abstract description 11
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims abstract description 11
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims abstract description 8
- 239000004202 carbamide Substances 0.000 claims abstract description 8
- 208000027531 mycobacterial infectious disease Diseases 0.000 claims abstract description 8
- 208000019693 Lung disease Diseases 0.000 claims abstract description 7
- 206010062207 Mycobacterial infection Diseases 0.000 claims abstract description 7
- 208000035143 Bacterial infection Diseases 0.000 claims abstract description 5
- 230000001580 bacterial effect Effects 0.000 claims abstract description 5
- 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 5
- 210000004369 blood Anatomy 0.000 claims abstract description 4
- 239000008280 blood Substances 0.000 claims abstract description 4
- 241000894006 Bacteria Species 0.000 abstract description 12
- 208000035473 Communicable disease Diseases 0.000 abstract description 4
- 239000002207 metabolite Substances 0.000 description 32
- 239000000090 biomarker Substances 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 5
- 201000008827 tuberculosis Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 208000032376 Lung infection Diseases 0.000 description 3
- 238000007621 cluster analysis Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 230000036470 plasma concentration Effects 0.000 description 3
- 241000193830 Bacillus <bacterium> Species 0.000 description 2
- 241001508003 Mycobacterium abscessus Species 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- FGEPRNXUNITOCW-UHFFFAOYSA-N 2-aminobutanal Chemical compound CCC(N)C=O FGEPRNXUNITOCW-UHFFFAOYSA-N 0.000 description 1
- 241000304886 Bacilli Species 0.000 description 1
- 241001105445 Mycobacterium abscessus subsp. massiliense Species 0.000 description 1
- 241000186367 Mycobacterium avium Species 0.000 description 1
- 206010058806 Mycobacterium avium complex infection Diseases 0.000 description 1
- 241001302239 Mycobacterium tuberculosis complex Species 0.000 description 1
- 206010031252 Osteomyelitis Diseases 0.000 description 1
- 206010062255 Soft tissue infection Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 230000001355 anti-mycobacterial effect Effects 0.000 description 1
- 239000003926 antimycobacterial agent Substances 0.000 description 1
- 150000001483 arginine derivatives Chemical class 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000000104 diagnostic biomarker Substances 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 201000003265 lymphadenitis Diseases 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 238000006241 metabolic reaction Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000000513 principal component analysis Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 208000015891 sexual disease Diseases 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
Classifications
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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
- G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
-
- 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
Abstract
본 발명은 비결핵 항산균 폐질환 의심 환자가 비결핵 항산균에 의한 감염 질환인지를 신속하게 확인하기 위한 정보제공방법과 진단용 키트에 관한 것으로서, 보다 상세하게는 비결핵 항산균 폐질환 의심 환자의 혈액 중의 아르기닌, 글루타민, 라이신, 트립토판, 유레아 및 4-아미노부탄알로 이루어지는 군에서 하나 또는 둘 이상의 농도를 측정하는 것을 특징으로 하는 비결핵 항산균 감염여부 진단을 위한 정보제공방법과, 아르기닌, 글루타민, 라이신 및 트립토판으로 이루어지는 군에서 하나 또는 둘 이상의 농도를 측정하는 장치를 포함하는, 비결핵 항산균 감염여부 진단용 키트에 관한 것이다.The present invention relates to an information provision method and diagnostic kit for quickly confirming whether a patient suspected of non-tuberculous acid-fast bacterial lung disease has an infectious disease caused by non-tuberculous acid-fast bacteria. More specifically, the present invention relates to a diagnostic kit for a patient suspected of non-tuberculous acid-fast bacterial lung disease. An information provision method for diagnosing non-tuberculous mycobacterial infection characterized by measuring the concentration of one or two or more from the group consisting of arginine, glutamine, lysine, tryptophan, urea, and 4-aminobutanal in the blood, and arginine, glutamine, It relates to a kit for diagnosing nontuberculous acid-fast bacterial infection, including a device for measuring the concentration of one or more of two or more from the group consisting of lysine and tryptophan.
Description
본 발명은 비결핵 항산균 폐질환 의심 환자가 비결핵 항산균에 의한 감염 질환인지를 신속하게 확인하기 위한 정보제공방법과 진단용 키트에 관한 것이다. The present invention relates to a method for providing information and a diagnostic kit for quickly confirming whether a patient suspected of having non-tuberculous acid-fast bacterial lung disease has an infectious disease caused by non-tuberculous acid-fast bacteria.
비결핵 항산균(non-tuberculous mycobacteria; NTM)에 의한 감염의 발생률, 유병률 및 사망률은 전 세계적으로 급속히 증가하고 있다. 비결핵 항산균성 폐질환(NTM pulmonary diseases; NTM-PDs)은 NTM 감염의 가장 빈번한 임상 증상으로, 느리게 성장하는 Mycobacterium avium (Mav) 복합체와 빠르게 성장하는 M. abscessus 복합체에 의해 발생한다. The incidence, prevalence, and mortality of infections caused by non-tuberculous mycobacteria (NTM) are rapidly increasing worldwide. Non-tuberculous mycobacterial pulmonary diseases (NTM-PDs) are the most frequent clinical manifestations of NTM infections and are caused by the slow-growing Mycobacterium avium (Mav) complex and the fast-growing M. abscessus complex.
일반적으로, NTM-PD에 대한 치료 기간은 12개월 이상으로, 본래적 또는 획득된 항생제 내성으로 그 치료과정이 복잡하고 집중적인데 반해 결과가 좋지 않은 경우가 많다. 최근 전세계적으로 비결핵 항산균에 기인한 폐 감염 보고가 증가하고 있어 비결핵 항산균 폐 감염 질환자를 신속하게 구별하기 위한 방법이나 바이오마커에 관한 연구가 요청되고 있다. In general, the treatment period for NTM-PD is more than 12 months, and the treatment process is complex and intensive due to inherent or acquired antibiotic resistance, but the results are often poor. Recently, reports of lung infections caused by non-tuberculous acid-fast bacteria have been increasing worldwide, and research on methods or biomarkers to quickly distinguish patients with non-tuberculous acid-fast bacteria lung infections is being requested.
등록특허 10-2270398(비결핵 항산균에 의한 감염 질환을 구별하기 위한 바이오마커)은 대상체에게 발병한 비결핵 항산균에 의한 감염 질환의 종류를 구별 진단하기 위한 바이오마커와, 상기 구별 진단을 위한 키트 또는 구별 진단 방법에 관한 것이다. 그러나 이 문헌은 그 실시예에 명확하게 기재되어 있듯이, 사전에 "마이코박테리움 아비움 복합체(Mycobacterium avium complex) 감염"이라는 것이 확인된 상태에서 폐 질환, 림프절염, 피부·연조직·골감염증 또는 파종성 질환 등 관련 질환들 중 구체적으로 어떤 질환인지를 구별하여 진단하는 바이오마커에 관한 것이다.Registered patent 10-2270398 (biomarker for distinguishing infectious diseases caused by non-tuberculous acid-fast bacteria) is a biomarker for distinguishing and diagnosing the type of infectious disease caused by non-tuberculous acid-fast bacteria in a subject, and Relates to a kit or differential diagnostic method. However, as this document clearly states in its examples, lung disease, lymphadenitis, skin, soft tissue, and bone infection, or disseminated disease, with “ Mycobacterium avium complex infection” confirmed in advance. It concerns biomarkers that distinguish and diagnose specific diseases among related diseases, such as sexual diseases.
미국등록특허 US 8580490(Markers for screening anti-mycobacterial treatment efficacy)은 아르기닌 유도체 등 대사체 농도 변화로부터 결핵의 치료 효과를 확인하는 마커에 관한 것이다. 그러나 이는 비결핵 항산균 감염여부의 진단에 관한 것이 아니라 결핵균(Mycobacterium tuberculosis complex) 감염에 의한 결핵의 치료효과를 확인하기 위한 것이다. US registered patent US 8580490 (Markers for screening anti-mycobacterial treatment efficacy) relates to markers that confirm the treatment effect of tuberculosis from changes in the concentration of metabolites such as arginine derivatives. However, this is not about diagnosing non-tuberculous acid-fast bacteria infection, but rather about confirming the treatment effect of tuberculosis caused by Mycobacterium tuberculosis complex infection.
본 발명은 비결핵 항산균 감염 여부를 신속하고 정확하게 확인할 수 있는 방법 및 이를 위한 진단용 키트를 제공하는 것을 목적으로 한다.The purpose of the present invention is to provide a method for quickly and accurately confirming non-tuberculous mycobacterial infection and a diagnostic kit for the same.
전술한 목적을 달성하기 위한 본 발명은 비결핵 항산균 폐질환 의심 환자의 혈액 중의 아르기닌, 글루타민, 라이신, 트립토판, 유레아 및 4-아미노부탄알로 이루어지는 군에서 하나 또는 둘 이상의 농도를 측정하는 것을 특징으로 하는 비결핵 항산균 감염여부 진단을 위한 정보제공방법에 관한 것이다. The present invention for achieving the above-described object is characterized by measuring the concentration of one or two or more from the group consisting of arginine, glutamine, lysine, tryptophan, urea, and 4-aminobutanal in the blood of a patient suspected of non-tuberculous acid-fast bacterial lung disease. This is about a method of providing information for diagnosing non-tuberculous acid-fast bacterial infection.
이때 본 발명은, 4-아미노부탄알 및 라이신의 농도를 측정하는 것을 반드시 포함하는 것이 바람직하다. At this time, the present invention preferably includes measuring the concentrations of 4-aminobutanal and lysine.
본 발명은 또한 아르기닌, 글루타민, 라이신 및 트립토판으로 이루어지는 군에서 하나 또는 둘 이상의 농도를 측정하는 장치를 포함하는, 비결핵 항산균 감염여부 진단용 키트에 관한 것이다.The present invention also relates to a kit for diagnosing non-tuberculous mycobacterial infection, including a device for measuring the concentration of one or more of the group consisting of arginine, glutamine, lysine and tryptophan.
이때 상기 장치는, 4-아미노부탄알 및 라이신의 농도를 측정하는 것이 바람직하다.At this time, the device preferably measures the concentrations of 4-aminobutanal and lysine.
이상과 같이 본 발명에 의하면 신속하고 간편하며 경제적으로 비결핵 항산균(NTM) 감염 여부를 확인할 수 있다. 이에 따라 의료진이 환자에게 적절한 처치를 조기에 진행할 수 있게 되어 비결핵 항산균(NTM) 감염에 의한 피해를 최소화할 수 있게 된다.As described above, according to the present invention, non-tuberculous mycobacteria (NTM) infection can be confirmed quickly, easily, and economically. As a result, medical staff will be able to provide appropriate treatment to patients at an early stage, minimizing damage caused by non-tuberculosis mycobacteria (NTM) infection.
도 1a는 본 발명의 실시예에서 수행한 대사체 군집의 히트맵 도면.
도 1b는 본 발명의 실시예에서 대사체 군집 분석 결과 건강인 대조군과 비결핵 항산균 감염 환자 혈청간 대사체 변화를 보여주는 그래프.
도 1c는 본 발명의 실시예에서 대사체 군집 분석 결과 비결핵 항산균 환자군과 건강인 대조군 간 대사체들의 평균 존재 분포도.
도 2는 비결핵 항산균 환자나 건강인 대조군 개개인의 혈청에서 유의적 발현차이를 보이는 대사체의 농도 그래프.Figure 1a is a heatmap diagram of metabolite clusters performed in an example of the present invention.
Figure 1b is a graph showing metabolite changes between the serum of a healthy control group and a non-tuberculous acid-fast bacillus infected patient as a result of metabolite cluster analysis in an example of the present invention.
Figure 1c is a distribution chart of the average presence of metabolites between a non-tuberculous acid-fast bacillus patient group and a healthy control group as a result of metabolite cluster analysis in an example of the present invention.
Figure 2 is a graph of the concentration of metabolites showing significant expression differences in the serum of non-tuberculous acid-fast bacteria patients or healthy control individuals.
이하 첨부된 도면과 실시예를 들어 본 발명을 보다 상세히 설명한다. 그러나 이러한 도면과 실시예는 본 발명의 기술적 사상의 내용과 범위를 쉽게 설명하기 위한 예시일 뿐, 이에 의해 본 발명의 기술적 범위가 한정되거나 변경되는 것은 아니다. 이러한 예시에 기초하여 본 발명의 기술적 사상의 범위 안에서 다양한 변형과 변경이 가능함은 당업자에게는 당연할 것이다.Hereinafter, the present invention will be described in more detail with reference to the attached drawings and examples. However, these drawings and examples are merely examples for easily explaining the content and scope of the technical idea of the present invention, and the technical scope of the present invention is not limited or changed thereby. Based on these examples, it will be obvious to those skilled in the art that various modifications and changes are possible within the scope of the technical idea of the present invention.
본 발명자들은 건강한 사람과 비결핵 항산균 폐 감염 질환자 혈청의 대사체 분석을 통해 다음을 확인하였다. The present inventors confirmed the following through metabolite analysis of the serum of healthy people and patients with non-tuberculosis mycobacterial lung infection disease.
ⓐ NTM-PD 환자에서 4-아미노부탄알, 유레아, 트립토판 농도가 유의적으로 증가함ⓐ Concentrations of 4-aminobutanal, urea, and tryptophan were significantly increased in NTM-PD patients.
ⓑ NTM-PD 환자에서 아르기닌, 글루타민, 라이신 농도가 유의적으로 감소함ⓑ Arginine, glutamine, and lysine concentrations were significantly decreased in NTM-PD patients.
본 발명은 이러한 발견에 기초한 것으로서, 아르기닌, 글루타민, 라이신, 트립토판, 유레아, 4-아미노부탄알을 바이오마커로 활용하여 잠재적 환자로부터 신속하고 정확하게 비결핵 항산균 감염 여부를 확인할 수 있는 방법 및 진단용 키트에 관한 것이다.The present invention is based on these findings, and is a method and diagnostic kit for quickly and accurately confirming non-tuberculous mycobacterial infection in a potential patient by using arginine, glutamine, lysine, tryptophan, urea, and 4-aminobutanal as biomarkers. It's about.
아래 실시예에서는 대사체 농도를 측정하기 위한 시료로 혈청을 사용하였으나 전혈 또는 혈장을 시료로 할 수도 있다. 또한 정확한 측정을 위해 예를 들면, 여과, 증류, 추출, 분리, 농축, 방해 성분의 불활성화, 시약의 첨가 등의 전처리 단계가 추가될 수도 있다. In the examples below, serum was used as a sample to measure metabolite concentration, but whole blood or plasma may also be used as a sample. Additionally, for accurate measurement, pretreatment steps such as filtration, distillation, extraction, separation, concentration, inactivation of interfering components, and addition of reagents may be added.
[실시예][Example]
1. 혈청을 대상으로 한 대사체 분석1. Metabolite analysis of serum
비결핵 항산균의 종류에 따라 M. abscessus 환자군(Mabc ; n=16), M. massiliense 환자군(Mmass ; n=16)과 건강인 대조군(HC ; n=20) 혈청의 비표적 대사체 분석을 진행하였다. According to the type of non-tuberculous acid-fast bacteria, non-targeted metabolite analysis was performed on the serum of M. abscessus patients (Mabc; n=16), M. massiliense patients (Mmass; n=16), and healthy control group (HC; n=20). proceeded.
대사체의 군집 변화를 비중심 Pearson's 상관법과 중심 연결 군집분석을 통해 분석하고 MetaboAnalyst (v5.0)로 도식화하여 도 1a에 도시하였다. 도면에서 행(raw)은 시험군의 각 개체이며, 열(column)은 분석된 207종의 대사체(대사체의 명칭은 도시 생략)이다. 도면에서 데이터는 log2 scale이다. Clustered Heatmap은 대사체들을 변수로 하여 어떻게 이 변수들이 각 조건들 사이에서 얼마나 독립적으로 비슷한지 아니면 다른 지를 평가할 수 있는 방법이다. Cluster changes in metabolites were analyzed using non-central Pearson's correlation and central link cluster analysis, and were plotted using MetaboAnalyst (v5.0) and shown in Figure 1a. In the figure, the rows (raw) represent each individual in the test group, and the columns represent the 207 metabolites analyzed (the names of the metabolites are not shown). The data in the figure is log 2 scale. Clustered Heatmap is a method that uses metabolites as variables to independently evaluate how similar or different these variables are between each condition.
이를 바탕으로 한 2차원 주성분 분석결과, 건강인 대조군과 비결핵 항산균 환자군의 대사 작용이 다른 변화를 나타냄을 확인하였다(도 1b 참조). As a result of two-dimensional principal component analysis based on this, it was confirmed that the metabolic activity of the healthy control group and the non-tuberculous acid-fast bacteria patient group showed different changes (see Figure 1b).
Metlin 데이터베이스(http://metlin.scripps.edu)를 토대로 비결핵 항산균 질환 환자와 건강인 간 대사체 상관관계를 Fold chain 분석과 표적 대사체 분석을 통하여 규명하였다. 그 결과, Tryptophan을 비롯한 124개의 대사체가 유의하게 증가한 반면, arginine과 glutamine 를 포함하는 23개의 대사체가 유의하게 감소되어 있음을 확인하였다(도 1c 참조). 도면은 Log fold change의 산점도를 통하여 비결핵 항산균 환자군과 건강인 대조군 간 대사체들의 평균 존재 분포도 즉, 대사체들의 양적인 차이를 도표화 한 것이다. 유의하게 증가한 대사체(Up)는 빨간색, 감소한 대사체(down)는 파란색, 차이가 없는 것(Unsig)은 회색 점으로 표현하였다. 환자군과 정상인 대조군 그룹 간에 특정 대사체들의 전체적인 대사반응이 다름을 확인할 수 있다. Based on the Metlin database (http://metlin.scripps.edu), the metabolite correlation between non-tuberculosis mycobacterial disease patients and healthy subjects was identified through fold chain analysis and targeted metabolite analysis. As a result, it was confirmed that 124 metabolites, including Tryptophan, were significantly increased, while 23 metabolites, including arginine and glutamine, were significantly decreased (see Figure 1c). The figure plots the distribution of the average presence of metabolites between the non-tuberculous acid-fast bacteria patient group and the healthy control group through a scatter plot of log fold change, that is, the quantitative difference in metabolites. Significantly increased metabolites (Up) are expressed in red, decreased metabolites (Down) are expressed in blue, and those with no difference (Unsig) are expressed in gray dots. It can be seen that the overall metabolic reactions of specific metabolites are different between the patient group and the normal control group.
2. 바이오마커의 선정2. Selection of biomarkers
대사체 분석을 통해 혈장 중의 수준에 유의한 증가나 감소가 나타나는 147개 대사체 중 혈장 중 절대 농도가 높고 환자군과 건강인 대조군 사이의 편차가 큰 대사체를 선별하였다. Through metabolite analysis, among 147 metabolites that showed significant increases or decreases in plasma levels, metabolites with high absolute plasma concentrations and large differences between the patient group and the healthy control group were selected.
그 결과 유의하게 증가하는 대사체 중에서는 4-아미노부탄알(4-aminobutanal), 유레아(urea) 및 트립토판(tryptophan)이, 유의하게 감소하는 대사체 중에서는 아르기닌(arginine), 글루타민(glutamine) 및 라이신(lysine)이 선정되었다. As a result, among the metabolites that significantly increased, 4-aminobutanal, urea, and tryptophan, and among the metabolites that significantly decreased, arginine, glutamine, and Lysine was selected.
이들 6종의 대사체에 대한 비결핵 항산균 환자와 건강인 대조군 개개인의 혈장내 농도를 도 2에 도시하였다. 도면에서 막대그래프는 대사체 군집의 크기를 나타내며, ion count (y축)로 개개인을 표현하였다. (통계 방법은 Students' t-test 검정을 이용, ***, P<0.001로 표현함)The plasma concentrations of these six metabolites in non-tuberculous acid-fast bacilli patients and healthy control individuals are shown in Figure 2. In the figure, the bar graph represents the size of the metabolite cluster, and each individual is represented by ion count (y-axis). (Statistical method uses Students' t-test test, expressed as ***, P<0.001)
도 2에서 볼 수 있듯이 4-아미노부탄알, 유레아, 트립토판, 아르기닌 및 글루타민이 비결핵 항산균 감염 환자에서 그 발현이 유의적으로 증가하거나 감소하는 것을 확인하였다. As can be seen in Figure 2, the expression of 4-aminobutanal, urea, tryptophan, arginine, and glutamine was confirmed to be significantly increased or decreased in patients with non-tuberculous mycobacterial infection.
이상의 결과를 종합하면 이들 대사체가 비결핵 항산균 환자의 진단 바이오마커로써 활용될 수 있음을 의미한다. 특히 아미노부탄알과 라이신은 환자군과 대조군 사이에 농도차이가 명확하면서 개체간 농도 겹침이 나타나지 않기 때문에 비결핵 항산균 감염 여부를 확인하는 바이오마커로 매우 유용할 것이다.Taken together, the above results mean that these metabolites can be used as diagnostic biomarkers for non-tuberculous acid-fast bacteria patients. In particular, aminobutanal and lysine will be very useful as biomarkers to confirm non-tuberculous mycobacterial infection because there is a clear difference in concentration between the patient group and the control group and no overlap in concentration between individuals.
Claims (4)
For diagnosing non-tuberculous acid-fast bacterial infection, characterized by measuring the concentration of one or two or more from the group consisting of arginine, glutamine, lysine, tryptophan, urea, and 4-aminobutanal in the blood of a patient suspected of non-tuberculous acid-fast bacterial lung disease. How to provide information.
4-아미노부탄알 및 라이신의 농도를 측정하는 것을 포함하는, 비결핵 항산균 감염여부 진단을 위한 정보제공방법.
In claim 1,
A method of providing information for diagnosing nontuberculous acid-fast bacterial infection, including measuring the concentrations of 4-aminobutanal and lysine.
A kit for diagnosing non-tuberculous mycobacterial infection, comprising a device for measuring the concentration of one or more of the following: arginine, glutamine, lysine, tryptophan, urea, and 4-aminobutanal.
상기 장치는, 4-아미노부탄알 및 라이신의 농도를 측정하는 것을 특징으로 하는 비결핵 항산균 감염여부 진단용 키트.In claim 3,
The device is a kit for diagnosing non-tuberculous acid-fast bacterial infection, characterized in that it measures the concentration of 4-aminobutanal and lysine.
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| KR102270398B1 (en) | 2019-11-25 | 2021-06-29 | 주식회사 큐라티스 | Biomarker for classifying nontuberculous mycobacteria infection diseases |
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