JP2023063389A - Method for assisting in detection of primary bile cholangitis - Google Patents
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- 238000000034 method Methods 0.000 title claims abstract description 28
- 238000001514 detection method Methods 0.000 title claims abstract description 7
- 208000003167 cholangitis Diseases 0.000 title abstract description 5
- 210000000941 bile Anatomy 0.000 title abstract 4
- 108010028554 LDL Cholesterol Proteins 0.000 claims abstract description 88
- 239000008280 blood Substances 0.000 claims abstract description 34
- 210000004369 blood Anatomy 0.000 claims abstract description 34
- 238000012360 testing method Methods 0.000 claims abstract description 11
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 79
- 208000012654 Primary biliary cholangitis Diseases 0.000 claims description 79
- -1 sdLDL-C Proteins 0.000 claims description 2
- 238000009534 blood test Methods 0.000 abstract description 3
- 230000000052 comparative effect Effects 0.000 description 40
- 230000035945 sensitivity Effects 0.000 description 16
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 12
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 108010023302 HDL Cholesterol Proteins 0.000 description 6
- 235000012000 cholesterol Nutrition 0.000 description 6
- 208000010152 Huntington disease-like 3 Diseases 0.000 description 3
- 108010007622 LDL Lipoproteins Proteins 0.000 description 3
- 102000007330 LDL Lipoproteins Human genes 0.000 description 3
- 238000000691 measurement method Methods 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 238000008214 LDL Cholesterol Methods 0.000 description 2
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- 102000004895 Lipoproteins Human genes 0.000 description 2
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- 150000002632 lipids Chemical class 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- 101000856500 Bacillus subtilis subsp. natto Glutathione hydrolase proenzyme Proteins 0.000 description 1
- 206010008635 Cholestasis Diseases 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 238000000585 Mann–Whitney U test Methods 0.000 description 1
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- 150000004716 alpha keto acids Chemical class 0.000 description 1
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- 108010030696 low density lipoprotein triglyceride Proteins 0.000 description 1
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- 210000002381 plasma Anatomy 0.000 description 1
- 208000037920 primary disease Diseases 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
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- 108091008012 small dense LDL Proteins 0.000 description 1
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- 150000003626 triacylglycerols Chemical class 0.000 description 1
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Abstract
Description
本発明は、血液検査により、原発性胆汁性胆管炎の検出を補助する方法に関する。 The present invention relates to a blood test to aid in the detection of primary biliary cholangitis.
従来、原発性胆汁性胆管炎(PBC)は組織学的所見や、血液所見で慢性の胆汁うっ滞所見（ALP, γ-GTP の上昇）や抗ミトコンドリア抗体（AMA）陽性所見で診断されていたが、その診断方法は複雑であった。 Traditionally, primary biliary cholangitis (PBC) was diagnosed based on histological findings, chronic cholestasis findings (ALP, γ-GTP elevation), and antimitochondrial antibody (AMA) positive findings on blood findings. However, the diagnostic method was complicated.
本発明の目的は、血液検査により、簡便にPBCを検出することを補助する方法を提供することである。 An object of the present invention is to provide a method for easily assisting detection of PBC by a blood test.
本願発明者らは、鋭意研究の結果、生体から分離された被検血液試料中の、LDL-TG、RLP-C、LDL-TG/LDL-C、sd LDL-C、LDL-C/sd LDL-C、LDL-TG/sd LDL-C、総TG及び総TG/総CHOから成る群より選ばれる少なくとも１種を指標としてPBCを検出することを補助することが可能であることを見出し、本発明を完成した。 As a result of intensive research, the inventors of the present application found that LDL-TG, RLP-C, LDL-TG/LDL-C, sd LDL-C, LDL-C/sd LDL in a test blood sample separated from a living body -C, LDL-TG/sd LDL-C, total TG and total TG/total CHO. completed the invention.
すなわち、本発明は、以下のものを提供する。
（１）生体から分離された被検血液試料中の、LDL-TG、RLP-C、LDL-TG/LDL-C、sd LDL-C、LDL-C/sd LDL-C、LDL-TG/sd LDL-C、総TG及び総TG/総CHOから成る群より選ばれる少なくとも１種を測定することを含む、原発性胆汁性胆管炎の検出を補助する方法。
（２）LDL-TG量を指標とし、健常者よりもLDL-TG量が高いことが、原発性胆汁性胆管炎である可能性が高いことを示す、（１）記載の方法。
（３）RLP-C量を指標とし、健常者よりもRLP-C量が高いことが、原発性胆汁性胆管炎である可能性が高いことを示す、（１）記載の方法。
（４）LDL-TG/LDL-C比を指標とし、健常者よりもLDL-TG/LDL-C比が高いことが、原発性胆汁性胆管炎である可能性が高いことを示す、（１）記載の方法。
（５）sd LDL-C量を指標とし、健常者よりもsd LDL-C量が高いことが、原発性胆汁性胆管炎である可能性が高いことを示す、（１）記載の方法。
（６）LDL-C/sd LDL-C比を指標とし、健常者よりもLDL-C/sd LDL-C比が低いことが、原発性胆汁性胆管炎である可能性が高いことを示す、（１）記載の方法。
（７）LDL-TG/sd LDL-C比を指標とし、健常者よりもLDL-TG/sd LDL-C比が低いことが、原発性胆汁性胆管炎である可能性が高いことを示す、（１）記載の方法。
（８）総TG量を指標とし、健常者よりも総TG量が高いことが、原発性胆汁性胆管炎である可能性が高いことを示す、（１）記載の方法。
（９）総TG/総CHO比を指標とし、健常者よりも総TG/総CHO比が高いことが、原発性胆汁性胆管炎である可能性が高いことを示す、（１）記載の方法。
That is, the present invention provides the following.
(1) LDL-TG, RLP-C, LDL-TG/LDL-C, sd LDL-C, LDL-C/sd LDL-C, LDL-TG/sd in a test blood sample separated from a living body A method for assisting detection of primary biliary cholangitis, comprising measuring at least one selected from the group consisting of LDL-C, total TG and total TG/total CHO.
(2) The method according to (1), wherein the LDL-TG level is used as an index, and a higher LDL-TG level than that in a healthy subject indicates a high possibility of primary biliary cholangitis.
(3) The method according to (1), wherein the RLP-C level is used as an index, and a higher RLP-C level than in healthy subjects indicates a high possibility of primary biliary cholangitis.
(4) Using the LDL-TG/LDL-C ratio as an index, a higher LDL-TG/LDL-C ratio than in healthy subjects indicates a high possibility of primary biliary cholangitis (1 ) described method.
(5) The method according to (1), wherein the sd LDL-C level is used as an indicator, and a higher sd LDL-C level than in healthy subjects indicates a high possibility of primary biliary cholangitis.
(6) Using the LDL-C/sd LDL-C ratio as an index, a lower LDL-C/sd LDL-C ratio than in healthy subjects indicates a high possibility of primary biliary cholangitis. (1) The method described.
(7) Using the LDL-TG/sd LDL-C ratio as an index, a lower LDL-TG/sd LDL-C ratio than in healthy subjects indicates a high possibility of primary biliary cholangitis. (1) The method described.
(8) The method according to (1), wherein the total TG level is used as an indicator, and a higher total TG level than in healthy subjects indicates a high possibility of primary biliary cholangitis.
(9) The method according to (1), wherein the ratio of total TG/total CHO is used as an index, and a higher ratio of total TG/total CHO than in healthy subjects indicates a high possibility of primary biliary cholangitis. .
本発明において、「TG」はトリグリセライド（中性脂肪ともいう）、「LDL-TG」は低密度リポ蛋白質中のトリグリセライド、「sd LDL-C」は小粒子低密度リポ蛋白質中のコレステロール、「RLP-C」はレムナント様リポ蛋白質中のコレステロール、「LDL-C」は、低密度リポ蛋白質中のコレステロール、「CHO」はコレステロールを意味する。なお、これらの略号は、血中脂質の分野において通常用いられている略号である。 In the present invention, "TG" is triglyceride (also referred to as neutral fat), "LDL-TG" is triglyceride in low density lipoprotein, "sd LDL-C" is cholesterol in small particle low density lipoprotein, "RLP -C" means cholesterol in remnant-like lipoproteins, "LDL-C" means cholesterol in low-density lipoproteins, and "CHO" means cholesterol. These abbreviations are commonly used in the field of blood lipids.
血液試料としては、全血、血清又は血漿を用いることができる。 Whole blood, serum or plasma can be used as the blood sample.
血液試料中の総TG、LDL-TG、sd LDL-C、RLP-C、LDL-C及び総CHOは、周知の方法により測定することができ、下記実施例にも測定方法が具体的に記載されている。 Total TG, LDL-TG, sd LDL-C, RLP-C, LDL-C and total CHO in blood samples can be measured by well-known methods, and the measurement methods are also specifically described in the examples below. It is
本発明において、総TG量を指標とする場合、健常者よりも総TG量が高いことが、PBCである可能性が高いことを示す。判定に用いるカットオフ値は、本発明を使用する者が求める感度、特異度に応じた範囲で適宜設定でき、例えば、50～158mg/dL範囲内であり、好ましくは96.0mg/dLの±20%の範囲内であり、最適値は96.0mg/dLであり、かつ、本発明を使用する者が求める感度、特異度に応じた値に設定することができる。なお、「カットオフ値」は、この値以上又は以下であれば、原発性胆汁性胆管炎である可能性が高いと判定する値である。統計学的処理として、カットオフ値の最適値はROC曲線の解析を行い、Youden's indexによって算出した。 In the present invention, when the total TG amount is used as an index, a higher total TG amount than in healthy subjects indicates a high possibility of PBC. The cut-off value used for determination can be appropriately set within a range according to the sensitivity and specificity required by the person using the present invention. %, the optimum value is 96.0 mg/dL, and the value can be set according to the sensitivity and specificity desired by the person using the present invention. The "cutoff value" is a value that determines that there is a high possibility of primary biliary cholangitis if it is above or below this value. As statistical processing, the optimum cutoff value was calculated by Youden's index after analyzing the ROC curve.
本発明において、LDL-TG量を指標とする場合、健常者よりもLDL-TG量が高いことが、PBCである可能性が高いことを示す。判定に用いるカットオフ値は、本発明を使用する者が求める感度、特異度に応じた範囲で適宜設定でき、例えば、10.0～20.5mg/dLの範囲内であり、好ましくは12.7mg/dL±20%の範囲内であり、最適値は12.7mg/dLであり、かつ、本発明を使用する者が求める感度、特異度に応じた値に設定することができる。 In the present invention, when the LDL-TG level is used as an index, a higher LDL-TG level than that in healthy subjects indicates a high possibility of PBC. The cut-off value used for determination can be appropriately set within a range according to the sensitivity and specificity required by the person using the present invention, for example, within the range of 10.0 to 20.5 mg / dL, preferably 12.7 mg / dL ± It is within the range of 20%, the optimum value is 12.7 mg/dL, and the value can be set according to the sensitivity and specificity desired by the person using the present invention.
本発明において、sd LDL-C量を指標とする場合、健常者よりもsd LDL-C量が高いことが、PBCである可能性が高いことを示す。判定に用いるカットオフ値は、本発明を使用する者が求める感度、特異度に応じた範囲で適宜設定でき、例えば、12.4～43.9mg/dLの範囲内であり、好ましくは21.2mg/dLの±20%の範囲内であり、最適値は21.2mg/dLであり、かつ、本発明を使用する者が求める感度、特異度に応じた値に設定することができる。 In the present invention, when the sd LDL-C level is used as an index, a higher sd LDL-C level than in healthy subjects indicates a high possibility of PBC. The cut-off value used for determination can be appropriately set within a range according to the sensitivity and specificity required by the person using the present invention, for example, within the range of 12.4 to 43.9 mg / dL, preferably 21.2 mg / dL The range is ±20%, the optimum value is 21.2 mg/dL, and the value can be set according to the sensitivity and specificity desired by the person using the present invention.
本発明において、RLP-C量を指標とする場合、健常者よりもRLP-C量が高いことが、PBCである可能性が高いことを示す。判定に用いるカットオフ値は、本発明を使用する者が求める感度、特異度に応じた範囲で適宜設定でき、例えば、1.4～3.7mg/dLの範囲内であり、好ましくは2.7mg/dL±20%の範囲内であり、最適値は2.7mg/dLであり、かつ、本発明を使用する者が求める感度、特異度に応じた値に設定することができる。 In the present invention, when the RLP-C amount is used as an index, a higher RLP-C amount than that in healthy subjects indicates a high possibility of PBC. The cut-off value used for determination can be appropriately set within a range according to the sensitivity and specificity required by the person using the present invention, for example, within the range of 1.4 to 3.7 mg / dL, preferably 2.7 mg / dL ± It is within the range of 20%, the optimum value is 2.7 mg/dL, and the value can be set according to the sensitivity and specificity desired by the person using the present invention.
本発明において、LDL-TG/LDL-C比を指標とする場合、健常者よりもLDL-TG/LDL-C比が高いことが、PBCである可能性が高いことを示す。判定に用いるカットオフ値は、本発明を使用する者が求める感度、特異度に応じた範囲で適宜設定でき、例えば、0.104～0.193の範囲内であり、好ましくは0.134±20%の範囲内であり、最適値は0.134であり、かつ、本発明を使用する者が求める感度、特異度に応じた値に設定することができる。 In the present invention, when the LDL-TG/LDL-C ratio is used as an index, a higher LDL-TG/LDL-C ratio than healthy subjects indicates a high possibility of PBC. The cut-off value used for determination can be appropriately set within the range according to the sensitivity and specificity required by the person using the present invention, for example, within the range of 0.104 to 0.193, preferably within the range of 0.134 ± 20% The optimum value is 0.134, and the value can be set according to the sensitivity and specificity desired by the person using the present invention.
本発明において、総TG/総CHO比を指標とする場合、健常者よりも総TG/総CHO比が高いことが、PBCである可能性が高いことを示す。判定に用いるカットオフ値は、本発明を使用する者が求める感度、特異度に応じた範囲で適宜設定でき、例えば、0.229～1.171の範囲内であり、好ましくは0.523±20%の範囲内であり、最適値は0.523であり、かつ、本発明を使用する者が求める感度、特異度に応じた値に設定することができる。 In the present invention, when the total TG/total CHO ratio is used as an index, a higher total TG/total CHO ratio than that in healthy subjects indicates a high possibility of PBC. The cut-off value used for determination can be appropriately set within a range according to the sensitivity and specificity required by the person using the present invention. The optimum value is 0.523, and the value can be set according to the sensitivity and specificity desired by the person using the present invention.
本発明において、LDL-C/sd LDL-C比を指標とする場合、健常者よりもLDL-C/sdLDL-C比が低いことが、PBCである可能性が高いことを示す。判定に用いるカットオフ値は、本発明を使用する者が求める感度、特異度に応じた範囲で適宜設定でき、例えば、2.67～7.04の範囲内であり、好ましくは5.16±20%の範囲内であり、最適値は5.16であり、かつ、本発明を使用する者が求める感度、特異度に応じた値に設定することができる。 In the present invention, when the LDL-C/sd LDL-C ratio is used as an index, a lower LDL-C/sdLDL-C ratio than that in healthy subjects indicates a high possibility of PBC. The cut-off value used for determination can be appropriately set within a range according to the sensitivity and specificity required by the person using the present invention, for example, within the range of 2.67 to 7.04, preferably within the range of 5.16 ± 20% The optimum value is 5.16, and the value can be set according to the sensitivity and specificity desired by the person using the present invention.
本発明において、LDL-TG/sd LDL-C比を指標とする場合、健常者よりもLDL-TG/sd LDL-C比が低いことが、PBCである可能性が高いことを示す。判定に用いるカットオフ値は、本発明を使用する者が求める感度、特異度に応じた範囲で適宜設定でき、例えば、1.12～3.04の範囲内であり、好ましくは1.74±20%の範囲内であり、最適値は1.74であり、かつ、本発明を使用する者が求める感度、特異度に応じた値に設定することができる。 In the present invention, when the LDL-TG/sd LDL-C ratio is used as an index, a lower LDL-TG/sd LDL-C ratio than in healthy subjects indicates a high possibility of PBC. The cut-off value used for determination can be appropriately set within a range according to the sensitivity and specificity required by the person using the present invention, for example, within the range of 1.12 to 3.04, preferably within the range of 1.74 ± 20% The optimum value is 1.74, and the value can be set according to the sensitivity and specificity desired by the person using the present invention.
以下、本発明を実施例に基づき具体的に説明する。もっとも、本発明は下記実施例に限定されるものではない。 EXAMPLES The present invention will be specifically described below based on examples. However, the present invention is not limited to the following examples.
なお、下記実施例又は比較例において採用した、各脂質の具体的な測定方法は次のとおりであった。
１．総TGの測定方法
総TG量は臨床検査の場で用いられている自動分析装置を用いてトリグリセリド測定用試薬であるTG-EX「生研」（酵素法）（デンカ生研社製）により測定した。
Specific methods for measuring each lipid employed in the following Examples and Comparative Examples were as follows.
1. Measurement method of total TG The amount of total TG was measured with TG-EX “SEIKEN” (enzyme method) (manufactured by Denka Seiken Co., Ltd.), which is a reagent for measuring triglycerides, using an automatic analyzer used in clinical examinations.
２．LDL-TGの測定方法
LDL-TG量は臨床検査の場で用いられている自動分析装置を用いてＬＤＬ－トリグリセライド測定用試薬であるＬＤＬＴＧ－ＥＸ“ＳＥＩＫＥＮ”（デンカ生研社製）により測定した。
2. How to measure LDL-TG
The amount of LDL-TG was measured with LDLTG-EX “SEIKEN” (manufactured by Denka Seiken Co., Ltd.), which is a reagent for measuring LDL-triglyceride, using an automatic analyzer used in clinical examinations.
３．sd LDL-Cの測定方法
sd LDL-C量は自動分析装置を用いてsd LDL-コレステロール測定用試薬であるsd LDL-EX「生研」（デンカ生研社製）により測定した。
3. How to measure sd LDL-C
The amount of sd LDL-C was measured using an automatic analyzer using sd LDL-EX "SEIKEN" (manufactured by Denka Seiken Co., Ltd.), which is a reagent for measuring sd LDL-cholesterol.
４．RLP-Cの測定方法
RLP-C量は自動分析装置を用いてRLP-コレステロール測定用試薬により測定した。RLP-コレステロール測定用試薬は、以下の参考文献に記載の方法で調製した。
（参考文献）Hirao Y, Nakajima K, Machida T, Murakami M, Ito Y. Development of a Novel Homogeneous Assay for Remnant Lipoprotein Particle Cholesterol. The Journal of Applied Laboratory Medicine 2018;03:26-36
4. How to measure RLP-C
The amount of RLP-C was measured with an RLP-cholesterol measuring reagent using an automatic analyzer. A reagent for measuring RLP-cholesterol was prepared by the method described in the following references.
(Reference) Hirao Y, Nakajima K, Machida T, Murakami M, Ito Y. Development of a Novel Homogeneous Assay for Remnant Lipoprotein Particle Cholesterol. The Journal of Applied Laboratory Medicine 2018;03:26-36
５．LDL-Cの測定方法
LDL-C量は臨床検査の場で用いられている自動分析装置を用いてLDL-コレステロール測定用試薬である自動分析用試薬「生研」LDL-EX(N)（直接法）（デンカ生研社製）により測定した。
5. How to measure LDL-C
The amount of LDL-C was measured using an automatic analyzer used in clinical testing, which is a reagent for measuring LDL-cholesterol. ).
６．総CHOの測定方法
総CHO量は臨床検査の場で用いられている自動分析装置を用いてコレステロール測定用試薬である自動分析用試薬「生研」T-CHO(S)（酵素法）（デンカ生研社製）により測定した。
6. Measurement method of total CHO The total CHO amount was measured using an automatic analyzer used in clinical testing, using an automatic analysis reagent "Seiken" T-CHO (S) (enzyme method) (Denka Seiken), which is a reagent for measuring cholesterol. company).
また、2群間の比較は、Shapiro-Wilkの検定でノンパラメトリックだった場合にWilcoxon-Mann-Whitney検定を行い、パラメトリックだった場合に等分散検定を行った上でStudentのt検定もしくはWelchのt検定を行った。 For comparison between the two groups, the Wilcoxon-Mann-Whitney test was performed when the Shapiro-Wilk test was nonparametric, and when the test was parametric, the Student's t-test or Welch's test was performed after performing the equal variance test. A t-test was performed.
比較例１（LDL-C）
対応のない、健常者（図においてHealthと表記）48名、PBC患者48名からなる全96名の集団から採取した血液中のLDL-C量を測定し、それぞれの群を比較した。比較したグラフを図１に示す。その結果、PBC患者群は、健常者群と比べてLDL-C量に差はなかった。
Comparative Example 1 (LDL-C)
The amount of LDL-C in the blood sampled from a total of 96 unmatched groups consisting of 48 healthy subjects (denoted as Health in the figure) and 48 PBC patients was measured, and the respective groups were compared. A comparative graph is shown in FIG. As a result, there was no difference in the amount of LDL-C between the PBC patient group and the healthy subject group.
比較例２（HDL3-C）
対応のない、健常者（図においてHealthと表記）48名、PBC患者48名からなる全96名の集団から採取した血液中のHDL3-C量を測定し、それぞれの群を比較した。比較したグラフを図２に示す。その結果、PBC患者群は、健常者群と比べてHDL3-C量に差はなかった。
Comparative Example 2 (HDL3-C)
The HDL3-C levels in the blood sampled from a total of 96 unmatched groups consisting of 48 healthy subjects (denoted as Health in the figure) and 48 PBC patients were measured, and the respective groups were compared. A comparative graph is shown in FIG. As a result, there was no difference in the amount of HDL3-C between the PBC patient group and the healthy subject group.
比較例３（総CHO）
対応のない、健常者（図においてHealthと表記）48名、PBC患者48名からなる全96名の集団から採取した血液中のT-CHO量を測定し、それぞれの群を比較した。比較したグラフを図３に示す。その結果、PBC患者群は、健常者群と比べてT-CHO量が高い傾向を示したが、統計学的有意差は認められなかった。
Comparative Example 3 (total CHO)
The amount of T-CHO in the blood sampled from a total of 96 unmatched groups consisting of 48 healthy subjects (indicated as Health in the figure) and 48 PBC patients was measured, and the respective groups were compared. A comparative graph is shown in FIG. As a result, the PBC patient group tended to have a higher amount of T-CHO than the healthy subject group, but no statistically significant difference was observed.
比較例４（HDL-C）
対応のない、健常者（図においてHealthと表記）48名、PBC患者48名からなる全96名の集団から採取した血液中のHDL-C量を測定し、それぞれの群を比較した。比較したグラフを図４に示す。その結果、PBC患者群は、健常者群と比べてHDL-C量が高い傾向を示したが、統計学的有意差は認められなかった。
Comparative Example 4 (HDL-C)
The amount of HDL-C in the blood sampled from a total of 96 unmatched groups consisting of 48 healthy subjects (denoted as Health in the figure) and 48 PBC patients was measured, and the respective groups were compared. A comparative graph is shown in FIG. As a result, the PBC patient group tended to have higher HDL-C levels than the healthy subject group, but no statistically significant difference was observed.
比較例５（HDL2-C）
対応のない、健常者（図においてHealthと表記）48名、PBC患者48名からなる全96名の集団から採取した血液中のHDL2-C量を測定し、それぞれの群を比較した。比較したグラフを図５に示す。その結果、PBC患者群は、健常者群と比べてHDL2-C量が高い傾向を示したが、統計学的有意差は認められなかった。
Comparative Example 5 (HDL2-C)
The amount of HDL2-C in the blood collected from a total of 96 unmatched groups consisting of 48 healthy subjects (denoted as Health in the figure) and 48 PBC patients was measured, and the respective groups were compared. A comparative graph is shown in FIG. As a result, the PBC patient group tended to have higher HDL2-C levels than the healthy subject group, but no statistically significant difference was observed.
実施例１（総TG）
対応のない、健常者（図においてHealthと表記）48名、PBC患者48名からなる全96名の集団から採取した血液中の総TG量を測定し、それぞれの群を比較した。比較したグラフを図６に示す。その結果、PBC患者群は、健常者群と比べて総TG量が統計学的に有意に高かった（p<0.0001）。
Example 1 (Total TG)
The total amount of TG in the blood sampled from a total of 96 unmatched groups consisting of 48 healthy subjects (indicated as Health in the figure) and 48 PBC patients was measured, and the respective groups were compared. A comparative graph is shown in FIG. As a result, the total TG amount was statistically significantly higher in the PBC patient group than in the healthy subject group (p<0.0001).
実施例２（LDL-TG）
対応のない、健常者（図においてHealthと表記）48名、PBC患者48名からなる全96名の集団から採取した血液中のLDL-TG量を測定し、それぞれの群を比較した。比較したグラフを図７に示す。その結果、PBC患者群は、健常者群と比べてLDL-TG量が統計学的に有意に高かった（p<0.0001）。
Example 2 (LDL-TG)
LDL-TG levels in blood sampled from a total of 96 unmatched groups consisting of 48 healthy subjects (denoted as Health in the figure) and 48 PBC patients were measured, and the respective groups were compared. A comparative graph is shown in FIG. As a result, the LDL-TG level was statistically significantly higher in the PBC patient group than in the healthy subject group (p<0.0001).
実施例３（sd LDL-C）
対応のない、健常者（図においてHealthと表記）48名、PBC患者48名からなる全96名の集団から採取した血液中のsd LDL-C量を測定し、それぞれの群を比較した。比較したグラフを図８に示す。その結果、PBC患者群は、健常者群と比べてsd LDL-C量が統計学的に有意に高かった（p<0.001）。
Example 3 (sdLDL-C)
The amount of sd LDL-C in the blood sampled from a total of 96 unmatched groups consisting of 48 healthy subjects (denoted as Health in the figure) and 48 PBC patients was measured, and the respective groups were compared. A comparative graph is shown in FIG. As a result, the sd LDL-C amount was statistically significantly higher in the PBC patient group than in the healthy subject group (p<0.001).
実施例４（RLP-C）
対応のない、健常者（図においてHealthと表記）48名、PBC患者48名からなる全96名の集団から採取した血液中のRLP-C量を測定し、それぞれの群を比較した。比較したグラフを図９に示す。その結果、PBC患者群は、健常者群と比べてRLP-C量が統計学的に有意に高かった（p<0.0001）。
Example 4 (RLP-C)
The amount of RLP-C in blood sampled from a total of 96 unmatched groups consisting of 48 healthy subjects (denoted as Health in the figure) and 48 PBC patients was measured, and the respective groups were compared. A comparative graph is shown in FIG. As a result, the amount of RLP-C was statistically significantly higher in the PBC patient group than in the healthy subject group (p<0.0001).
実施例５（LDL-TG/LDL-C）
対応のない、健常者（図においてHealthと表記）48名、PBC患者48名からなる全96名の集団から採取した血液中のLDL-TG量とLDL-C量を測定してLDL-TG／LDL-C比を算出し、それぞれの群を比較した。比較したグラフを図１０に示す。その結果、PBC患者群は、健常者群と比べてLDL-TG/LDL-C比が統計学的に有意に高かった（p<0.0001）。
Example 5 (LDL-TG/LDL-C)
LDL-TG and LDL-C levels in the blood collected from a total of 96 unmatched subjects, consisting of 48 healthy subjects (denoted as Health in the figure) and 48 PBC patients, were measured and LDL-TG/LDL-TG/ The LDL-C ratio was calculated and compared between each group. A comparative graph is shown in FIG. As a result, the LDL-TG/LDL-C ratio was statistically significantly higher in the PBC patient group than in the healthy subject group (p<0.0001).
実施例６（総TG/総CHO）
対応のない、健常者（図においてHealthと表記）48名、PBC患者48名からなる全96名の集団から採取した血液中の総TG量と総CHO量を測定して総TG／総CHO比を算出し、それぞれの群を比較した。比較したグラフを図１１に示す。その結果、PBC患者群は、健常者群と比べて総TG/総CHO比が統計学的に有意に高かった（p<0.0005）。
Example 6 (total TG/total CHO)
The total TG/total CHO ratio was obtained by measuring the total TG and total CHO levels in the blood collected from a total of 96 unmatched subjects, consisting of 48 healthy subjects (denoted as Health in the figure) and 48 PBC patients. was calculated and compared for each group. A comparative graph is shown in FIG. As a result, the total TG/total CHO ratio was statistically significantly higher in the PBC patient group than in the healthy control group (p<0.0005).
実施例７（LDL-C/sd LDL-C）
対応のない、健常者（図においてHealthと表記）48名、PBC患者48名からなる全96名の集団から採取した血液中のLDL-C量とsd LDL-C量を測定してLDL-C/sd LDL-C比を算出し、それぞれの群を比較した。比較したグラフを図１２に示す。その結果、PBC患者群は、健常者群と比べてLDL-C/sd LDL-C比が統計学的に有意に低かった（p<0.0001）。
Example 7 (LDL-C/sd LDL-C)
LDL-C and sd LDL-C levels in the blood collected from a total of 96 unmatched subjects, consisting of 48 healthy subjects (denoted as Health in the figure) and 48 PBC patients, were measured and LDL-C The /sd LDL-C ratio was calculated and compared between each group. A comparative graph is shown in FIG. As a result, the LDL-C/sd LDL-C ratio was statistically significantly lower in the PBC patient group than in the healthy subject group (p<0.0001).
実施例８（LDL-TG/sd LDL-C）
対応のない、健常者（図においてHealthと表記）48名、PBC患者48名からなる全96名の集団から採取した血液中のLDL-TG量とsd LDL-C量を測定してLDL-TG/sd LDL-C比を算出し、それぞれの群を比較した。比較したグラフを図１３に示す。その結果、PBC患者群は、健常者群と比べてLDL-TG/sd LDL-C比が統計学的に有意に低かった（p<0.005）。
Example 8 (LDL-TG/sd LDL-C)
LDL-TG levels and sd LDL-C levels in the blood collected from a total of 96 unmatched subjects, consisting of 48 healthy subjects (denoted as Health in the figure) and 48 PBC patients, were measured and LDL-TG levels were measured. The /sd LDL-C ratio was calculated and compared between each group. A comparative graph is shown in FIG. As a result, the LDL-TG/sd LDL-C ratio was statistically significantly lower in the PBC patient group than in the healthy subject group (p<0.005).
比較例６（総CHO）
対応のない、健常者（図においてHealthと表記）27名、PBC患者25名からなる全52名の集団から採取した血液中の総CHO量を測定し、それぞれの群を比較した。比較したグラフを図１４に示す。その結果、PBC患者群は、健常者群と比べて総CHO量に差はなかった。
Comparative Example 6 (total CHO)
The total amount of CHO in the blood sampled from a total of 52 unmatched groups consisting of 27 healthy subjects (denoted as Health in the figure) and 25 PBC patients was measured, and the respective groups were compared. A comparative graph is shown in FIG. As a result, there was no difference in the total amount of CHO between the PBC patient group and the healthy control group.
比較例７（HDL-C）
対応のない、健常者（図においてHealthと表記）27名、PBC患者25名からなる全52名の集団から採取した血液中のHDL-C量を測定し、それぞれの群を比較した。比較したグラフを図１５に示す。その結果、PBC患者群は、健常者群と比べてHDL-C量に差はなかった。
Comparative Example 7 (HDL-C)
The amount of HDL-C in the blood sampled from a total of 52 unmatched groups consisting of 27 healthy subjects (denoted as Health in the figure) and 25 PBC patients was measured, and the respective groups were compared. A comparative graph is shown in FIG. As a result, there was no difference in the amount of HDL-C between the PBC patient group and the healthy subject group.
比較例８（HDL2-C）
対応のない、健常者（図においてHealthと表記）27名、PBC患者25名からなる全52名の集団から採取した血液中のHDL2-C量を測定し、それぞれの群を比較した。比較したグラフを図１６に示す。その結果、PBC患者群は、健常者群と比べてHDL2-C量に差はなかった。
Comparative Example 8 (HDL2-C)
The amount of HDL2-C in the blood sampled from a total of 52 unmatched groups consisting of 27 healthy subjects (denoted as Health in the figure) and 25 PBC patients was measured, and the respective groups were compared. A comparative graph is shown in FIG. As a result, there was no difference in the amount of HDL2-C between the PBC patient group and the healthy subject group.
実施例９（総TG）
対応のない、健常者（図においてHealthと表記）27名、PBC患者25名からなる全52名の集団から採取した血液中の総TG量を測定し、それぞれの群を比較した。比較したグラフを図１７に示す。その結果、PBC患者群は、健常者群と比べて総TG量が統計学的に有意に高かった（p<0.005）。
Example 9 (Total TG)
The total amount of TG in the blood sampled from a total of 52 unmatched groups consisting of 27 healthy subjects (denoted as Health in the figure) and 25 PBC patients was measured, and the respective groups were compared. A comparative graph is shown in FIG. As a result, the total TG amount was statistically significantly higher in the PBC patient group than in the healthy subject group (p<0.005).
実施例１０（LDL-TG）
対応のない、健常者（図においてHealthと表記）27名、PBC患者25名からなる全52名の集団から採取した血液中のLDL-TG量を測定し、それぞれの群を比較した。比較したグラフを図１８に示す。その結果、PBC患者群は、健常者群と比べてLDL-TG量が統計学的に有意に高かった（p<0.0001）。
Example 10 (LDL-TG)
The amount of LDL-TG in the blood sampled from a total of 52 unmatched groups consisting of 27 healthy subjects (denoted as Health in the figure) and 25 PBC patients was measured, and the respective groups were compared. A comparative graph is shown in FIG. As a result, the LDL-TG level was statistically significantly higher in the PBC patient group than in the healthy subject group (p<0.0001).
実施例１１（RLP-C）
対応のない、健常者（図においてHealthと表記）27名、PBC患者25名からなる全52名の集団から採取した血液中のRLP-C量を測定し、それぞれの群を比較した。比較したグラフを図１９に示す。その結果、PBC患者群は、健常者群と比べてRLP-C量が統計学的に有意に高かった（p<0.0005）。
Example 11 (RLP-C)
The amount of RLP-C in the blood sampled from a total of 52 unmatched groups consisting of 27 healthy subjects (denoted as Health in the figure) and 25 PBC patients was measured, and the respective groups were compared. A comparative graph is shown in FIG. As a result, the amount of RLP-C was statistically significantly higher in the PBC patient group than in the healthy subject group (p<0.0005).
実施例１２（LDL-TG/LDL-C）
対応のない、健常者（図においてHealthと表記）27名、PBC患者25名からなる全52名の集団から採取した血液中のLDL-TG量とLDL-C量を測定してLDL-TG／LDL-C比を算出し、それぞれの群を比較した。比較したグラフを図２０に示す。その結果、PBC患者群は、健常者群と比べてLDL-TG/LDL-C量が統計学的に有意に高かった（p<0.0001）。
Example 12 (LDL-TG/LDL-C)
LDL-TG and LDL-C levels in the blood collected from a total of 52 unmatched subjects, consisting of 27 healthy subjects (denoted as Health in the figure) and 25 PBC patients, were measured and LDL-TG/LDL-TG levels were measured. The LDL-C ratio was calculated and compared between each group. A comparative graph is shown in FIG. As a result, the LDL-TG/LDL-C amount was statistically significantly higher in the PBC patient group than in the healthy subject group (p<0.0001).
実施例１３（総TG/T-CHO）
対応のない、健常者（図においてHealthと表記）27名、PBC患者25名からなる全52名の集団から採取した血液中の総TG量と総CHO量を測定して総TG／総CHO比を算出し、それぞれの群を比較した。比較したグラフを図２１に示す。その結果、PBC患者群は、健常者群と比べて総TG/総CHO量が有意に高かった（p<0.005）。
Example 13 (Total TG/T-CHO)
The total TG/total CHO ratio was determined by measuring the total TG and total CHO levels in the blood collected from a total of 52 unmatched subjects, consisting of 27 healthy subjects (denoted as Health in the figure) and 25 PBC patients. was calculated and compared for each group. A comparative graph is shown in FIG. As a result, the total TG/total CHO amount was significantly higher in the PBC patient group than in the healthy control group (p<0.005).
実施例１４（LDL-C/sd LDL-C）
対応のない、健常者（図においてHealthと表記）27名、PBC患者25名からなる全52名の集団から採取した血液中のLDL-C量とsd LDL-C量を測定してLDL-C/sd LDL-C比を算出し、それぞれの群を比較した。比較したグラフを図２２に示す。その結果、PBC患者群は、健常者群と比べてLDL-C/sd LDL-C比が統計学的に有意に低かった（p<0.005）。
Example 14 (LDL-C/sd LDL-C)
LDL-C and sd LDL-C levels in the blood collected from a total of 52 unpaired subjects, consisting of 27 healthy subjects (denoted as Health in the figure) and 25 PBC patients, were measured. The /sd LDL-C ratio was calculated and compared between each group. A comparative graph is shown in FIG. As a result, the LDL-C/sd LDL-C ratio was statistically significantly lower in the PBC patient group than in the healthy subject group (p<0.005).
実施例１５（LDL-TG/sd LDL-C）
対応のない、健常者（図においてHealthと表記）27名、PBC患者25名からなる全52名の集団から採取した血液中のLDL-TG量とsd LDL-C量を測定してLDL-TG/sd LDL-C比を算出し、それぞれの群を比較した。比較したグラフを図２３に示す。その結果、PBC患者群は、健常者群と比べてLDL-TG/sd LDL-C比が統計学的に有意に低かった（p<0.01）。
Example 15 (LDL-TG/sd LDL-C)
LDL-TG and sd LDL-C levels in the blood collected from a total of 52 unmatched subjects, consisting of 27 healthy subjects (denoted as Health in the figure) and 25 PBC patients, were measured and LDL-TG levels were measured. The /sd LDL-C ratio was calculated and compared between each group. A comparative graph is shown in FIG. As a result, the LDL-TG/sd LDL-C ratio was statistically significantly lower in the PBC patient group than in the healthy subject group (p<0.01).
本願発明者らは、鋭意研究の結果、生体から分離された被検血液試料中の、LDL-TG/LDL-Cを指標としてPBCを検出することを補助することが可能であることを見出し、本発明を完成した。 As a result of intensive research, the inventors of the present application have found that it is possible to assist the detection of PBC using LDL-TG/LDL-C as an index in a test blood sample separated from a living body. We have completed the present invention.
すなわち、本発明は、 生体から分離された被検血液試料中の、LDL-TG/LDL-Cを測定することを含み、健常者よりもLDL-TG/LDL-C比が高いことが、原発性胆汁性胆管炎である可能性が高いことを示す、原発性胆汁性胆管炎の検出を補助する方法、を提供する。
That is, the present invention includes measuring LDL-TG/LDL-C in a test blood sample separated from a living body, and a higher LDL-TG/LDL-C ratio than that of a healthy subject indicates primary disease. Kind Code: A1 Methods are provided to assist in detecting primary biliary cholangitis that is indicative of probable biliary cholangitis.
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