JP3530239B2 - Diagnostic methods and efficacy evaluation methods - Google Patents
Diagnostic methods and efficacy evaluation methodsInfo
- Publication number
- JP3530239B2 JP3530239B2 JP30949994A JP30949994A JP3530239B2 JP 3530239 B2 JP3530239 B2 JP 3530239B2 JP 30949994 A JP30949994 A JP 30949994A JP 30949994 A JP30949994 A JP 30949994A JP 3530239 B2 JP3530239 B2 JP 3530239B2
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- JP
- Japan
- Prior art keywords
- urine
- rheumatism
- index
- methods
- diagnostic
- Prior art date
- Legal status (The legal status 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 status listed.)
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Links
- 238000002405 diagnostic procedure Methods 0.000 title description 14
- 238000011156 evaluation Methods 0.000 title description 5
- 210000002700 urine Anatomy 0.000 claims description 32
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 20
- 229940109239 creatinine Drugs 0.000 claims description 11
- 238000012360 testing method Methods 0.000 claims description 10
- 229940124597 therapeutic agent Drugs 0.000 claims description 9
- 101001076407 Homo sapiens Interleukin-1 receptor antagonist protein Proteins 0.000 claims description 5
- 229940119178 Interleukin 1 receptor antagonist Drugs 0.000 claims description 5
- 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 claims description 5
- 239000003407 interleukin 1 receptor blocking agent Substances 0.000 claims description 5
- 102100026018 Interleukin-1 receptor antagonist protein Human genes 0.000 description 36
- 101710144554 Interleukin-1 receptor antagonist protein Proteins 0.000 description 36
- 229940079593 drug Drugs 0.000 description 11
- 238000005259 measurement Methods 0.000 description 9
- 206010039073 rheumatoid arthritis Diseases 0.000 description 9
- 238000003018 immunoassay Methods 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 238000003745 diagnosis Methods 0.000 description 7
- 230000002485 urinary effect Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 238000002523 gelfiltration Methods 0.000 description 6
- 238000002965 ELISA Methods 0.000 description 5
- 102000000589 Interleukin-1 Human genes 0.000 description 5
- 108010002352 Interleukin-1 Proteins 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 230000002452 interceptive effect Effects 0.000 description 5
- 238000003127 radioimmunoassay Methods 0.000 description 4
- 238000004062 sedimentation Methods 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 208000025747 Rheumatic disease Diseases 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 230000003907 kidney function Effects 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000008157 ELISA kit Methods 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 238000009533 lab test Methods 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 230000000552 rheumatic effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- 208000006820 Arthralgia Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000019223 Interleukin-1 receptor Human genes 0.000 description 1
- 108050006617 Interleukin-1 receptor Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 206010042674 Swelling Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000003916 acid precipitation Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 229960000182 blood factors Drugs 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000012812 general test Methods 0.000 description 1
- 229940111120 gold preparations Drugs 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 230000006920 protein precipitation Effects 0.000 description 1
- 239000012857 radioactive material Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Investigating Or Analysing Biological Materials (AREA)
Description
【０００１】[0001]
【産業上の利用分野】本発明は、尿中のインターロイキ
ン−１受容体アンタゴニストを指標としたリウマチの診
断法およびリウマチ診断を行うための臨床検査用キット
並びにリウマチ治療剤の薬効評価法に関する。TECHNICAL FIELD The present invention relates to a diagnostic method for rheumatism using an interleukin-1 receptor antagonist in urine as an index, a clinical test kit for diagnosing rheumatism, and a drug efficacy evaluation method for a therapeutic agent for rheumatism.
【０００２】[0002]
【従来の技術】慢性関節リウマチはリウマチ性疾患の代
表的な疾患であり、発症の要因は種々挙げられているが
確定的なものは見い出されておらず、また決定的な治療
薬剤も存在しない。実際のリウマチの治療においては、
消炎鎮痛剤、金製剤、ステロイド剤、免疫抑制剤等のい
くつかの種類の治療剤を次々と使用してみてその患者に
効果のある薬剤を見つけだす薬剤治療法が行われてい
る。従ってリウマチの簡便な診断方法の開発は、リウマ
チ患者の早期発見のみならず、リウマチ治療剤の効果を
判定するために非常に重要である。現在の慢性関節リウ
マチの診断法としては、アメリカリウマチ学会の診断基
準が主に用いられているが、これは関節の痛み、腫脹や
炎症等の臨床症状、赤沈値、血中のリウマトイド因子や
Ｃ反応性蛋白質（ＣＲＰ）などを指標に行われている。
赤沈値や血中因子量を測定するには患者から採血する必
要があるため、より患者に好ましい測定法、例えば尿中
の因子を指標とした診断法等の開発が望まれている。BACKGROUND ART Rheumatoid arthritis is a typical disease of rheumatoid arthritis, and various factors for its onset are listed, but no definitive one has been found and no definitive therapeutic drug exists. . In the actual treatment of rheumatism,
There is a drug treatment method in which several types of therapeutic agents such as anti-inflammatory analgesics, gold preparations, steroids, and immunosuppressive agents are used one after another to find a drug effective for the patient. Therefore, development of a simple method for diagnosing rheumatism is very important not only for early detection of rheumatism patients, but also for determining the effect of therapeutic agents for rheumatism. As a current diagnostic method for rheumatoid arthritis, the diagnostic criteria of the American College of Rheumatology are mainly used, but these include joint pain, clinical symptoms such as swelling and inflammation, erythrocyte sedimentation level, rheumatoid factor in blood and C It is performed using reactive protein (CRP) as an index.
Since it is necessary to collect blood from a patient in order to measure the erythrocyte sedimentation level and the amount of blood factor, it is desired to develop a more preferable measurement method for the patient, for example, a diagnostic method using a factor in urine as an index.
【０００３】インターロイキン−１（ＩＬ−１）はマク
ロファージ等から産生される免疫調節作用や種々の生理
活性を有するサイトカインであり、その多様な作用は標
的細胞上の受容体を介して発現される。生体はＩＬ−１
による生理活性を調節するためにＩＬ−１受容体におい
てＩＬ−１と拮抗する物質、即ちＩＬ−１受容体アンタ
ゴニスト（ＩＬ−１ｒａ）を自ら産生して生体機能の調
整を行っている。Interleukin-1 (IL-1) is a cytokine produced from macrophages and having an immunomodulatory action and various physiological activities, and its various actions are expressed via receptors on target cells. . Living body is IL-1
In order to regulate the physiological activity by the, the substance that antagonizes IL-1 at the IL-1 receptor, that is, the IL-1 receptor antagonist (IL-1ra) is produced by itself to regulate the biological function.
【０００４】本発明者らは採血等による苦痛を患者に与
えることなく簡便且つ迅速にリウマチの診断を行うこと
ができる方法について研究を続けた結果、尿中のＩＬ−
１ｒａ値がリウマチの指標になることを見い出し本発明
を完成した。[0004] The present inventors continued their research on a method capable of simply and rapidly diagnosing rheumatism without causing the patient the pain of blood collection and the like, and as a result, IL-urinary urine was detected.
The present invention was completed by finding that the 1ra value serves as an index of rheumatism.
【０００５】[0005]
【発明が解決しようとする課題】本発明の目的は、従来
の診断法のように採血や煩雑な臨床所見の数値化を行う
ことなく、容易に入手できる患者の尿を用いてリウマチ
の診断やリウマチ治療剤の薬効評価が可能な方法および
リウマチ診断の臨床検査用測定キットを提供することに
ある。The object of the present invention is to diagnose rheumatism by using the urine of a patient who is easily available, without performing blood sampling or digitizing complicated clinical findings unlike conventional diagnostic methods. (EN) It is intended to provide a method capable of evaluating the efficacy of a therapeutic agent for rheumatism and a measurement kit for clinical tests for diagnosing rheumatism.
【０００６】[0006]
【課題を解決するための手段】本発明は尿中のＩＬ−１
ｒａを指標としたリウマチの診断法、同診断用測定キッ
トおよびリウマチ治療剤の薬効評価法に関する。尿中の
ＩＬ−１ｒａの測定は、通常当該分野で行われている方
法が利用でき、抗ＩＬ−１活性を指標としたバイオアッ
セイ法やエンザイムイムノアッセイ（ＥＬＩＳＡ）、ラ
ジオイムノアッセイ（ＲＩＡ）等を用いることができ
る。操作の簡便性、感度、放射性物質の使用による設備
等の点から、ＥＬＩＳＡが最も利用しやすい。上記イム
ノアッセイ系を用いる場合、尿中に測定系を妨害する物
質が存在するため、この低分子量の妨害物質を除去する
ためにゲル濾過法、限外濾過法、透析法、酸等による蛋
白沈澱法などの前処理を行うのが好ましく、操作の迅速
性や簡便性の点からゲル濾過法が最も好ましい。The present invention is directed to IL-1 in urine.
The present invention relates to a method for diagnosing rheumatism using ra as an index, a measurement kit for the diagnosis, and a method for evaluating the efficacy of a therapeutic agent for rheumatism. For the measurement of IL-1ra in urine, a method generally used in the art can be used, and a bioassay method using an anti-IL-1 activity as an index, an enzyme immunoassay (ELISA), a radioimmunoassay (RIA) or the like is used. be able to. ELISA is the most easy to use in terms of ease of operation, sensitivity, and equipment that uses radioactive materials. When the above-mentioned immunoassay system is used, substances that interfere with the measurement system are present in urine, and therefore gel filtration, ultrafiltration, dialysis, protein precipitation with acids, etc. are used to remove these low molecular weight interfering substances. It is preferable to carry out pretreatment such as, and the gel filtration method is most preferable from the viewpoint of quickness and simplicity of operation.
【０００７】尿中のＩＬ−１ｒａ濃度は、健常人でさえ
も検体によって差異が大きく、これは腎機能の違いを反
映したものと考えられた。そこで腎機能の状態をよく反
映するマーカーとして知られている尿中のクレアチニン
を測定し、ＩＬ−１ｒａ／クレアチニンの比を取ったと
ころ安定した値が得られたため、ＩＬ−１ｒａ値はこの
ようなクレアチニンとの比で表し評価するのが好まし
い。クレアチニンだけでなく、その他腎機能の状態を反
映する尿中マーカーを利用してもよい。[0007] The IL-1ra concentration in urine varied greatly depending on the sample even in a healthy person, which was considered to reflect the difference in renal function. Therefore, when creatinine in urine, which is known as a marker well reflecting the state of renal function, was measured and the ratio of IL-1ra / creatinine was calculated, a stable value was obtained. It is preferable to express it as a ratio with creatinine for evaluation. In addition to creatinine, other urinary markers that reflect the state of renal function may be used.
【０００８】本発明方法に関する好ましい実施態様を以
下に挙げる。
（１）尿中のＩＬ−１ｒａを指標としたリウマチ診断
法。
（２）ＩＬ−１ｒａをイムノアッセイ法（ＥＬＩＳＡ又
はＲＩＡ）で測定することを特徴とする上記診断法。
（３）イムノアッセイ法に対する尿中の妨害物質を除去
した後、ＩＬ−１ｒａをイムノアッセイ法で測定するこ
とを特徴とする上記診断法。
（４）ゲル濾過処理により尿中の妨害物質を除去するこ
とによる上記診断法。
（５）ＩＬ−１ｒａ／クレアチニン比で表した尿中ＩＬ
−１ｒａ値を用いる上記診断法。Preferred embodiments of the method of the present invention are listed below. (1) A rheumatism diagnostic method using IL-1ra in urine as an index. (2) The diagnostic method, wherein IL-1ra is measured by an immunoassay method (ELISA or RIA). (3) The above-mentioned diagnostic method, wherein IL-1ra is measured by an immunoassay method after removing interfering substances in urine for the immunoassay method. (4) The above diagnostic method by removing interfering substances in urine by gel filtration. (5) IL in urine expressed as IL-1ra / creatinine ratio
The above diagnostic method using a -1ra value.
【０００９】（６）尿中のＩＬ−１ｒａを測定してリウ
マチの診断を行うための臨床検査用キット。
（７）イムノアッセイ法キットである上記臨床検査用キ
ット。
（８）ＥＬＩＳＡキットである上記臨床検査用キット。
（９）上記（３）や（４）記載の尿処理を行い、次いで
ＩＬ−１ｒａをイムノアッセイ法で測定する上記臨床検
査用キット。(6) A clinical test kit for diagnosing rheumatism by measuring IL-1ra in urine. (7) The above clinical test kit which is an immunoassay kit. (8) The above clinical test kit, which is an ELISA kit. (9) The kit for clinical examination, which comprises performing the urine treatment described in (3) or (4) above and then measuring IL-1ra by an immunoassay method.
【００１０】（１０）尿中のＩＬ−１ｒａを指標とした
リウマチ治療剤の薬効評価法。
（１１）ＩＬ−１ｒａをイムノアッセイ法（ＥＬＩＳＡ
又はＲＩＡ）で測定することを特徴とする上記薬効評価
法。
（１２）上記（３）や（４）記載の尿処理を行い、次い
でＩＬ−１ｒａをイムノアッセイ法で測定する上記薬効
評価法。
（１３）ＩＬ−１ｒａ／クレアチニン比で表した尿中Ｉ
Ｌ−１ｒａ値を用いる上記薬効評価法。(10) A method for evaluating the efficacy of a therapeutic agent for rheumatism using IL-1ra in urine as an index. (11) IL-1ra was immunoassayed (ELISA
Or RIA). (12) The drug efficacy evaluation method as described above, wherein the urine treatment described in (3) or (4) above is performed, and then IL-1ra is measured by an immunoassay method. (13) Urinary I expressed by IL-1ra / creatinine ratio
The above-mentioned drug efficacy evaluation method using an L-1ra value.
【００１１】以下、実施例により本発明をより詳細に説
明する。Hereinafter, the present invention will be described in more detail with reference to examples.
１．ゲル濾過による前処理
前述したとおり、尿中にはＥＬＩＳＡに対する低分子量
妨害物質が存在するため、ゲル濾過法による前処理を行
って予め妨害物質を除去した。尿試料を遠心して沈澱を
除いた後、最終濃度０．１％になるようにウシ血清アル
ブミン（ＢＳＡ）を加え、これをセファデックスＧ−２
５（ファルマシア社製）の３ｍｌカラムに添加した。溶
出液としてリン酸緩衝化生理食塩液（Ｐｈｏｓｐｈａｔ
ｅ Ｂｕｆｆｅｒｅｄ Ｓａｌｔｓ、宝酒造株式会社
製）を用い、ＩＬ−１ｒａを含む蛋白質画分１ｍｌを分
画して得た。カラムは蛋白質の吸着を防ぐために６ｍｌ
の１％ＢＳＡを流しておき、リン酸緩衝化生理食塩液で
充分洗浄した後に使用した。本ゲル濾過法は、その他の
限外濾過法やトリクロロ酢酸沈澱法などと比べて、回収
率が高く最も好ましい前処理方法であった。1. Pretreatment by Gel Filtration As described above, since low molecular weight interfering substances against ELISA are present in urine, interfering substances were previously removed by pretreatment by gel filtration. After the urine sample was centrifuged to remove the precipitate, bovine serum albumin (BSA) was added to a final concentration of 0.1%, and this was added to Sephadex G-2.
5 (manufactured by Pharmacia) was added to a 3 ml column. Phosphate buffered saline (Phosphat) as eluent
e Buffered Salts, manufactured by Takara Shuzo Co., Ltd.) was used to fractionate 1 ml of a protein fraction containing IL-1ra. Column is 6 ml to prevent protein adsorption
1% BSA was allowed to flow and was thoroughly washed with a phosphate buffered physiological saline solution before use. This gel filtration method was the most preferable pretreatment method because of its high recovery rate as compared with other ultrafiltration methods and trichloroacetic acid precipitation methods.
【００１２】２．ＩＬ−１ｒａの測定
上述の方法で前処理した尿中のＩＬ−１ｒａの測定は、
ＩＬ−１ｒａ測定用ＥＬＩＳＡキット（アマシャム社又
はＲ＆Ｄ社製）を用いて行った。ＩＬ−１ｒａ量は尿中
クレアチニン量との比で表すのが好ましいため、同じ尿
試料のクレアチニンをクレアチニン−テストワコー（和
光純薬株式会社製）で測定し、ＩＬ−１ｒａ／クレアチ
ニンの比を取って尿中ＩＬ−１ｒａ値とした。尚、尿検
体は４℃で保存すれば少なくとも８週間はＩＬ−１ｒａ
値は変化せず安定であった。以下に結果の一例を示す。2. Measurement of IL-1ra The measurement of IL-1ra in urine pretreated by the method described above is
IL-1ra measurement ELISA kit (manufactured by Amersham or R & D) was used. Since the amount of IL-1ra is preferably expressed as a ratio with the amount of creatinine in urine, creatinine in the same urine sample is measured with creatinine-Test Wako (manufactured by Wako Pure Chemical Industries, Ltd.), and the ratio of IL-1ra / creatinine is calculated. Urinary IL-1ra value. If the urine sample is stored at 4 ° C for at least 8 weeks, IL-1ra
The value did not change and was stable. An example of the result is shown below.
【００１３】[0013]
１．健常人とリウマチ患者におけるＩＬ−１ｒａ値
８人の健常男子の尿検体についてＩＬ−１ｒａ値、即ち
ＩＬ−１ｒａ（ｐｇ／ｍｌ）／クレアチニン（ｍｇ／ｄ
ｌ）を求めた結果、２８．２５±３．１６（平均±標準
誤差）であった。これに対して、２３人の慢性関節リウ
マチ患者においては１３６．７±２４．４であり、明ら
かに慢性関節リウマチ患者のＩＬ−１ｒａ値は顕著に高
かった。1. IL-1ra values in healthy subjects and rheumatism patients IL-1ra values, ie, IL-1ra (pg / ml) / creatinine (mg / d) in urine specimens of eight healthy males
As a result of obtaining l), it was 28.25 ± 3.16 (mean ± standard error). On the other hand, in 23 patients with rheumatoid arthritis, the value was 136.7 ± 24.4, and the IL-1ra value in patients with rheumatoid arthritis was significantly high.
【００１４】２．臨床検査値との相関性
現在のリウマチ性疾患の臨床検査としては、赤血球数、
赤沈、生化学的パラメーターの測定等の一般検査、ＣＲ
Ｐ、リウマトイド因子等の免疫血清学的検査、病理組織
学的検査、Ｘ線検査などが行われている。また臨床学的
な慢性関節リウマチの活動性を評価する判定基準として
ランズバリー指数がよく用いられている。ランズバリー
指数は、朝のこわばり時間、関節点数、握力および赤沈
値等の項目から算定表を参考にして指数を算出するが、
合計の指数が高いほど慢性関節リウマチの活動性が高い
と判定する。本願発明者らはこのような従来からの診断
法と本発明方法を比較し相関関係を調べた。2. Correlation with clinical laboratory values Currently clinical laboratory tests for rheumatic diseases include red blood cell count,
General tests such as red sedimentation, measurement of biochemical parameters, CR
Immunoserologic tests such as P and rheumatoid factors, histopathological tests, and X-ray tests are performed. The Landsbury index is often used as a criterion for evaluating the clinical activity of rheumatoid arthritis. The Lansbury Index is calculated by referring to the calculation table based on items such as morning stiffness, joint points, grip strength, and red stagnation value.
The higher the total index, the higher the activity of rheumatoid arthritis. The inventors of the present application compared the conventional diagnostic method with the method of the present invention, and examined the correlation.
【００１５】上記慢性関節リウマチ患者のＩＬ−１ｒａ
値と、従来の臨床検査項目にある赤沈および血中のＣＲ
Ｐ値を比較したところ、ＩＬ−１ｒａ値が増加するほど
赤沈およびＣＲＰの値が低下する傾向が認められた。ま
たリウマチの治療による寛解の判定指標とされているラ
ンズバリー指数との相関性を調べたところ、ランズバリ
ー指数で寛解にあると判定された患者においては、該指
数とＩＬ−１ｒａ値との間には正の相関傾向がみられ
た。即ち、薬剤等によるリウマチ症状の治療によって寛
解傾向の高い患者では、尿中のＩＬ−１ｒａ値が高い傾
向にあり、リウマチ治療剤の治療効果の判定の指標とし
て尿中ＩＬ−１ｒａ値を利用することができる。IL-1ra of the rheumatoid arthritis patient
Value and CR in blood and red sediment in the conventional laboratory test items
When the P values were compared, it was observed that the red sedimentation and CRP values tended to decrease as the IL-1ra value increased. In addition, when the correlation with the Ransbury index, which is used as an index for the determination of remission due to the treatment of rheumatism, was examined, it was found that the index between the index and the IL-1ra value was increased in patients who were determined to be in remission with the Ransbury index. There was a positive correlation tendency in. That is, in patients with a high remission tendency due to treatment of rheumatic symptoms with drugs and the like, the urinary IL-1ra value tends to be high, and the urinary IL-1ra value is used as an index for determining the therapeutic effect of the rheumatic therapeutic agent. be able to.
【００１６】上述のとおり、健常人と比べて慢性関節リ
ウマチ患者では尿中のＩＬ−１ｒａ値が著しく高くリウ
マチの診断に利用できることが明らかとなった。本発明
のような尿中の因子を指標としたリウマチの診断法は、
採血等による患者への苦痛を与えることがなく、患者に
とってはより好ましい診断法である。確実な診断のため
にはランズバリー指数等を用いた臨床診断を行わなけれ
ばならないが、この診断はいくつかの臨床症状を点数化
する操作及び長期の診断期間が必要である。これに対し
て本発明方法による尿中のＩＬ−１ｒａ値を指標とした
リウマチ診断法は簡便且つ迅速な診断が可能であるた
め、上記臨床症状の診断を助ける簡便で早期な診断法の
一つとして有用である。As described above, it has been revealed that the rheumatoid arthritis patient has a significantly higher IL-1ra level in urine than that of a healthy person and can be used for the diagnosis of rheumatism. The method for diagnosing rheumatism using factors in urine as an index according to the present invention,
It is a more preferable diagnostic method for a patient without causing pain to the patient due to blood collection or the like. Although a clinical diagnosis using the Lansbury index or the like must be performed for a reliable diagnosis, this diagnosis requires an operation for scoring some clinical symptoms and a long diagnosis period. On the other hand, the rheumatoid diagnostic method using the IL-1ra value in urine as an index according to the method of the present invention enables simple and rapid diagnosis, and thus is one of the simple and early diagnostic methods that aid in the diagnosis of the above clinical symptoms. Is useful as
【００１７】リウマチの病態は多様であり患者によって
有効性を示す薬剤が異なっているため、治療において何
種類かの薬剤を試みて患者にとって最適な薬剤を選択す
る方法が必要であるが、現在のところ一つの薬剤の効果
を判定するためには、ランズバリー指数等を用いて数週
間から数カ月の期間が必要とされる。上述した結果に示
したように、薬剤等によるリウマチの治療によって高寛
解度の患者では尿中のＩＬ−１ｒａ値が高い傾向にある
ことから、尿中ＩＬ−１ｒａ値の測定はリウマチ治療剤
の治療効果の判定の指標としても利用することができ、
本発明方法は非常に有用性が高い。Since the pathological conditions of rheumatism are diverse and the effective drug differs depending on the patient, there is a need for a method of trying several kinds of drugs in treatment and selecting the most suitable drug for the patient. However, in order to judge the effect of one drug, a period of several weeks to several months is required using the Lansbury index or the like. As shown in the above results, since the urinary IL-1ra level tends to be high in patients with high remission due to the treatment of rheumatism with a drug or the like, the measurement of the urinary IL-1ra level can be performed using a therapeutic agent for rheumatism. It can also be used as an index for determining the therapeutic effect,
The method of the present invention is very useful.
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 特開 平５−222081（ＪＰ，Ａ) 特開 平５−112462（ＪＰ，Ａ) 特開 平６−30788（ＪＰ，Ａ) 特開 平６−206893（ＪＰ，Ａ) 特表 平４−501002（ＪＰ，Ａ) 特表 平６−509418（ＪＰ，Ａ) (58)調査した分野(Int.Cl.7，ＤＢ名) G01N 33/53 G01N 33/564 ＣＡ（ＳＴＮ)─────────────────────────────────────────────────── ─── Continuation of the front page (56) Reference JP-A-5-222081 (JP, A) JP-A-5-112462 (JP, A) JP-A-6-30788 (JP, A) JP-A-6- 206893 (JP, A) Tokumei HEI 4-501002 (JP, A) Tokumei Hyo 6-509418 (JP, A) (58) Fields investigated (Int.Cl. 7 , DB name) G01N 33/53 G01N 33 / 564 CA (STN)
Claims (4)
ゴニストを指標としたリウマチの検査法。1. A method for testing rheumatism using an interleukin-1 receptor antagonist in urine as an index.
ゴニストを指標としたリウマチ治療薬の薬効評価法。2. A method for evaluating the efficacy of a therapeutic agent for rheumatism, which uses an interleukin-1 receptor antagonist in urine as an index.
ゴニスト値をリウマチの指標として用いる方法。3. A method of using an interleukin-1 receptor antagonist level in urine as an index of rheumatism.
ゴニスト値と尿中のクレアチニン値の比をリウマチの指
標として用いる方法。4. A method of using a ratio between an interleukin-1 receptor antagonist level in urine and a creatinine level in urine as an index of rheumatism.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP30949994A JP3530239B2 (en) | 1994-11-17 | 1994-11-17 | Diagnostic methods and efficacy evaluation methods |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP30949994A JP3530239B2 (en) | 1994-11-17 | 1994-11-17 | Diagnostic methods and efficacy evaluation methods |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH08145994A JPH08145994A (en) | 1996-06-07 |
| JP3530239B2 true JP3530239B2 (en) | 2004-05-24 |
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| JP30949994A Expired - Fee Related JP3530239B2 (en) | 1994-11-17 | 1994-11-17 | Diagnostic methods and efficacy evaluation methods |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013073041A1 (en) | 2011-11-17 | 2013-05-23 | 株式会社Ｄｎａチップ研究所 | Method for determining rheumatoid arthritis activity indicator, and biomarker used therein |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1774328A1 (en) * | 2004-07-23 | 2007-04-18 | Novartis AG | Biomarkers for rheumatoid arthritis (ra) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013073041A1 (en) | 2011-11-17 | 2013-05-23 | 株式会社Ｄｎａチップ研究所 | Method for determining rheumatoid arthritis activity indicator, and biomarker used therein |
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| Publication number | Publication date |
|---|---|
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