JPH021558A - Method of diagnosing multiple sclerosis and substance thereof - Google Patents
Method of diagnosing multiple sclerosis and substance thereofInfo
- Publication number
- JPH021558A JPH021558A JP12548789A JP12548789A JPH021558A JP H021558 A JPH021558 A JP H021558A JP 12548789 A JP12548789 A JP 12548789A JP 12548789 A JP12548789 A JP 12548789A JP H021558 A JPH021558 A JP H021558A
- Authority
- JP
- Japan
- Prior art keywords
- multiple sclerosis
- lymphocyte
- patient
- negative
- antibody
- 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.)
- Pending
Links
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Landscapes
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
【発明の詳細な説明】
(発明の背景)
本発明は一般的には人間の多発性硬化症状の診断に関し
、更に詳しくは新規な抗原、抗体の製剤及び多発性硬化
症の診断に有用な新規な抗原及び抗体を含有する卑疫学
的試薬に関する。DETAILED DESCRIPTION OF THE INVENTION BACKGROUND OF THE INVENTION The present invention relates generally to the diagnosis of multiple sclerosis symptoms in humans, and more particularly to novel antigens, antibody preparations, and novel methods useful for the diagnosis of multiple sclerosis. The present invention relates to epidemiological reagents containing antigens and antibodies.
多発性硬化症(multiple 5clerosis
)は、しばしば伝染性硬化症とも呼ばれるが、形態的に
は脳及びを髄における脱髄の斑点により特徴づけられ、
また臨床学的には多くの徴候及び軽快と悪化との症状に
より特徴づけられる中枢神経系の進行の遅い疾病である
。multiple sclerosis
), often called infectious sclerosis, is morphologically characterized by patches of demyelination in the brain and spinal cord;
Clinically, it is a slow-progressing disease of the central nervous system characterized by many signs and symptoms that ebb and flow.
多発性硬化症の病因は、本質的には不明であって、該疾
病は自己免疫機構、スローウィルスによる感來、金属前
の如き毒物、髄素分裂要素の如き新陳代謝要素及び異常
な血液凝塊メカニズムに起因する血管病変等によるもの
とされている。The etiology of multiple sclerosis is essentially unknown, and the disease may be caused by autoimmune mechanisms, slow viral infections, toxins such as metals, metabolic factors such as myelin division factors, and abnormal blood clots. This is thought to be due to vascular lesions caused by the mechanism.
多発性硬化症状の種々の徴候の中には、知覚障害(特に
視覚)、肢節の痙れん性脱力、小脳性失調症、眼振、膀
胱機能障害、気分のイライラ、及びこれらの2種もしく
はそれ以上の組み合わせがある。Among the various manifestations of multiple sclerosis symptoms are sensory disturbances (especially vision), spastic limb weakness, cerebellar ataxia, nystagmus, bladder dysfunction, irritability, and two or more of these. There are more combinations than that.
病状の診断は、多発性硬化症の上記徴候及び他の疾病の
類似の徴候が重複するため、実際上不可能である。病状
の診断は多くの場合類似の徴候を生じる他の疾病の併発
を組織的に排除しながら、何年にも亘る諸種の徴候の軽
快と悪化という“古典的′°病歴を前提としてなされる
。Diagnosis of the condition is practically impossible due to the overlap of the above symptoms of multiple sclerosis and similar symptoms of other diseases. Diagnosis of a medical condition is often made on the premise of a ``classic'' medical history, consisting of remissions and worsening of various symptoms over many years, while systematically excluding the co-occurrence of other diseases that produce similar symptoms.
徴候の源としての、例えば頭蓋内の病変、大脳血管障害
、聴音神経腫、小脳性腫瘍、脳幹の膠腫、を肺腫瘍、筋
萎縮性側索硬化症、梅毒、悪性貧血、頚部を柱関節炎椎
間円板破裂、偏平頭底症及び遺伝性失調症を排除するた
めに、実質的コストとしばしば患者への不快を伴う、側
副テスト(Collateral testing)が
行われる。Sources of symptoms include, for example, intracranial lesions, cerebral vascular disorders, acoustic neuromas, cerebellar tumors, gliomas of the brainstem, lung tumors, amyotrophic lateral sclerosis, syphilis, pernicious anemia, cervical columnar arthritis. Collateral testing, which involves substantial cost and often discomfort to the patient, is performed to rule out disc rupture, platysma and hereditary ataxias.
多発性硬化症の初期の診断に有用な診断方法及び物質の
開発に、実質的な努力が向けられてきた。大脳髄液につ
いての膠状全試験での陽性の結果は、陽性診断を支持す
るものと考えられるが決定づけるものではない。大脳髄
液中のガンマ・グロブリンの上昇についての試験(この
試験は病状が進行した場合の診断を確証させる傾向があ
るが、初期の診断には手助けと−はならない)について
も同様のことが当てはまる。同様に、しばしば本疾病と
関連性を有する活発な脱髄はを髄液の基礎蛋白検定試験
における分析結果の上昇により示されるが、試験のレベ
ルは一度急性悪化が終わると急激に低下する。病状の存
在と、血清及び大脳髄液中の麻疹抗体の上昇したレベル
との間には、決定的ではないが相関関係が存在する。ま
た、ある研究者はある明瞭な形態学上の変化に対するリ
ンパ球の電子顕微鏡検査が多発性硬化症の診断のために
効果的な基礎を提供しうるであろうと提唱している。Substantial efforts have been directed toward developing diagnostic methods and materials useful for early diagnosis of multiple sclerosis. A positive result on the colloidal test for cerebral spinal fluid is considered to support a positive diagnosis, but is not conclusive. The same applies to tests for elevated gamma globulin in the cerebral spinal fluid (which tends to confirm the diagnosis in advanced stages of the disease, but is not helpful in early diagnosis). . Similarly, active demyelination, which is often associated with this disease, is indicated by elevated cerebrospinal fluid basal protein assays, but test levels decline rapidly once the acute exacerbation ends. An inconclusive correlation exists between the presence of pathology and elevated levels of measles antibodies in serum and cerebral spinal fluid. Some investigators have also proposed that electron microscopy of lymphocytes for certain distinct morphological changes may provide an effective basis for the diagnosis of multiple sclerosis.
当該技術分野における掻く最近の進歩は、アンジャース
(Angers)等による、1979年4月9日付の「
ケミカル・アンド・エンジニアリング・ニュース CC
hemicaJ & Engineering New
s)」の22ページの報告に例示されている。簡潔に要
約すれば、アンジャース等は病状が逆戻り又は進行中の
多発性硬化症患者の血液からの本質的に非特異的血液抽
出物(所謂、“多発性硬化症関連物質°′)を用いての
白血球凝集阻止(Leuko−cyte adhere
nce 1nhibitionHLAI)テストの有用
性を主張している。このLAIテストは、MSRM中で
の培養後にテストサンプル赤血球のガラス表面に付着す
る能力の減少を測定することを含む。このかなり複雑で
、時間を要する高価な操作は、多発性硬化症患者の確認
精度が約90%、また非多発性硬化症患者の確認精度が
約95%と言われている。Recent advances in the field are reviewed in Angers et al., April 9, 1979.
Chemical and Engineering News CC
hemicaJ & Engineering New
s)” on page 22. Briefly summarized, Angers et al. used essentially non-specific blood extracts (so-called "multiple sclerosis-related substances °') from the blood of multiple sclerosis patients whose disease is reversing or in progress. Inhibition of leukocyte aggregation (Leuko-cyte adhere)
nce 1nhibitionHLAI) test. This LAI test involves measuring the decrease in the ability of test sample red blood cells to adhere to a glass surface after incubation in MSRM. This rather complicated, time-consuming and expensive operation is said to have a confirmation accuracy of about 90% for multiple sclerosis patients and about 95% for non-multiple sclerosis patients.
かくして、当分野において多発性硬化症状の存在を迅速
に、簡潔に、正確に定める診断方法及び物質に対する極
めて実質的な要請が存在するのである。望ましくは、か
かる方法は多発性硬化症に高度に特異的なものであるべ
き(すなわち、他の中枢神経系疾病の場合に虚偽の陽性
結果を与えない)である。更にかかる方法は初期段階で
の病状の存在を確定しうるちのであるべきで、病気の悪
化や軽快とは無関係に使用できるべきであり、苦痛もし
くは危険を伴う患者の組織サンプルの除去(withd
rawals)操作を包含しないものであるべきで、更
にまた、好ましくは高価又は操作の困難な装置を要求し
ない標準化された研究室的技術からなるものであるべき
である。Thus, there is a very substantial need in the art for diagnostic methods and materials that quickly, simply, and accurately determine the presence of multiple sclerosis symptoms. Desirably, such methods should be highly specific for multiple sclerosis (ie, do not give false positive results in the case of other central nervous system diseases). Furthermore, such methods should be able to establish the presence of a disease state in its early stages, should be able to be used regardless of whether the disease is worsening or remitting, and should not require painful or dangerous removal of patient tissue samples.
Furthermore, it should preferably consist of standardized laboratory techniques that do not require expensive or difficult-to-operate equipment.
(簡単な要約)
本発明の主たる特徴によれば、多発性硬化症にかかって
いる患者のリンパ球と関連性を有する抗原物質と特異的
に免疫学的に反応する抗体が提供される。この抗体は該
疾病にががっている疑いのある患者から得たリンパ球に
応用される標準化免疫学的評価での使用に好適な診断用
試薬を開発するために用いられる。BRIEF SUMMARY According to the main features of the present invention, antibodies are provided that specifically immunologically react with antigenic substances associated with lymphocytes of patients suffering from multiple sclerosis. This antibody will be used to develop diagnostic reagents suitable for use in standardized immunological evaluations applied to lymphocytes from patients suspected of suffering from the disease.
本発明の他の特徴及び利点は、以下の詳細な説明を考慮
するならば当業者に明らかとなろう。Other features and advantages of the invention will be apparent to those skilled in the art upon consideration of the following detailed description.
(詳細な説明)
本発明の実施上の根拠は、少なくとも部分的には多発性
硬化症にかかっていると臨床的に診断された患者の血液
(主としてリンパ球)と特異的な関連性を有する抗原物
質の発見にある。DETAILED DESCRIPTION The basis for the practice of the present invention is, at least in part, to have a specific association with the blood (primarily lymphocytes) of patients clinically diagnosed as suffering from multiple sclerosis. It lies in the discovery of antigenic substances.
更にこの抗原は免疫学的に活性な異種動物(例、うさぎ
)でも特異的抗体の定量的な形成を促進し得ることが見
出された。このようにして生成した特異的抗体を含有す
る試料は、リンパ球のサンプリング時点での患者の軽快
もしくは悪化の状態又は病気の進行段階とは本質的に無
関係に、多発性硬化症患者のリンパ球と免疫学的に反応
することが見出された。重要なことは、この抗体の製剤
は本質的に非多発性硬化症患者、多発性硬化症に関連し
て、しばしば誤診される中枢神経系疾病にかかった患者
でさえも免疫学的に反応しないことである。Furthermore, it has been found that this antigen can promote the quantitative formation of specific antibodies even in immunologically active xenospecies animals (eg rabbits). Samples containing specific antibodies generated in this manner are used to detect lymphocytes from multiple sclerosis patients, essentially independent of the patient's remission or deterioration status or stage of disease progression at the time of lymphocyte sampling. was found to immunologically react with Importantly, this antibody formulation is essentially immunologically unresponsive in non-MS patients, even those with central nervous system diseases associated with MS and often misdiagnosed. That's true.
本発明の抗体は、免疫拡散検定、螢光抗体検定、放射線
免疫検定等を含む各種の免疫学的操作において好適に用
いられ、その各々はかかる用途に適した試薬の開発を包
含することになろう。The antibodies of the present invention are suitably used in various immunological procedures, including immunodiffusion assays, fluorescent antibody assays, radiation immunoassays, etc., each of which involves the development of reagents suitable for such uses. Dew.
以下に記す実施例は、ある最近の好適な操作に従った本
発明の実施を例示する。更に詳しくは、それらの実施例
は抗原接種物として又は患者テストサンプルとしてのい
ずれかに使用されるリンパ球の調製、特異的抗体の開発
、及び免疫拡散検定における抗体の用途を取り扱う。The examples set forth below illustrate the practice of the invention according to certain currently preferred operations. More specifically, the examples address the preparation of lymphocytes for use either as antigen inocula or as patient test samples, the development of specific antibodies, and the use of antibodies in immunodiffusion assays.
実施例1゜
抗体を開発するための抗原接種物として用いられるリン
パ球及び本発明による診断テストで用いられるリンパ球
は、以下に例示する操作によって調製される。10m1
の静脈血サンプルが脱気されたチューブに集められ、例
えば0.5mlの0.1Mクエン酸ナトリウムと十分に
混合される。Example 1 Lymphocytes used as antigen inoculum for developing antibodies and in diagnostic tests according to the invention are prepared by the procedures exemplified below. 10m1
A sample of venous blood is collected in a degassed tube and mixed thoroughly with, for example, 0.5 ml of 0.1 M sodium citrate.
リンパ球はリンパ球調製培地(Lymphocyte
Pr−eparation Medium ;バイオネ
テイクス(Bione−tics) )を用いて血液か
ら分離され、定速で遠心分離され、リンパ球層は除去さ
れる。細胞は均質化され細胞膜も破砕し、均質化された
リンパ球は必要とされる時まで(−80°Cで)保存さ
れる。かかるリンパ球調製の抗原成分は極めて安定で、
少なくとも8力月間は冷凍温度で免疫学的に“無傷(i
ntact)”の状態にあり、少なくとも4回の“冷凍
−解凍″゛サイクル−80°Cから22°Cの)に耐え
ることができる。Lymphocytes are prepared using lymphocyte preparation medium (Lymphocyte
It is separated from the blood using Pre-eparation Medium (Bionetics), centrifuged at constant speed, and the lymphocyte layer is removed. The cells are homogenized, the cell membranes are disrupted, and the homogenized lymphocytes are stored (at -80°C) until needed. The antigenic components of such lymphocyte preparations are extremely stable;
Immunologically “intact” (i.e.
ntact) and can withstand at least four "freeze-thaw" cycles (from 80°C to 22°C).
実施例2゜
本発明の抗体は、以下の例示的操作により得られる。実
施例1.に従って調製され、多発性硬化症と臨床的に診
断された1人又はそれ以上の患者から得られた6mlの
均質化リンパ球が4mlのフロイント完全補助液(Fr
eund’s CompleteAdjuvant)に
加えられ、混合して安定なサスペンションとする。各々
のうさぎにリンパ球/補助液サスペンション(各々2匹
ずつ)の0.5ml筋肉注射を4回施し、補助液の添加
のない均質化リンパ球1mlが耳の周辺静脈に投与され
る。Example 2 Antibodies of the present invention are obtained by the following exemplary procedure. Example 1. 6 ml of homogenized lymphocytes obtained from one or more patients clinically diagnosed with multiple sclerosis were mixed with 4 ml of Freund's complete supplement (Fr.
eund's Complete Adjuvant) and mixed into a stable suspension. Each rabbit receives four 0.5 ml intramuscular injections of the lymphocyte/supplementary fluid suspension (two animals each) and 1 ml of homogenized lymphocytes without the addition of supplementary fluid is administered into the peripheral ear vein.
筋肉注射は最初の接種から7日、14日、21日後に繰
り返される。最後の注射から2週間後、うさぎは犠牲と
され、血液は心臓穿刺により除去される。Intramuscular injections are repeated 7, 14, and 21 days after the initial inoculation. Two weeks after the last injection, the rabbits are sacrificed and blood is removed by cardiac puncture.
血清は血液全体から分離され、精製にかけられ、非特異
的抗体及び特に多発性硬化症抗原成分以外の人間のリン
パ球組成に反応して動物の中にできた非特異的抗体を除
去する。この分離は、例えば非疾病患者(コントロール
)からのリンパ球均質化物との連続的な吸収接触により
達成される。1時間当たり4回の連続接触で、例えば3
7℃でコントロールリンパ球均質化物の部分標本1ml
で処理された4mlの、血清サンプルで血清を“純粋″
′にするのに十分である。このようにして得られた抗体
は全く安定である。予備的な電気泳動分析は特異的多発
性硬化症抗体がマイクロ・グロブリンらしきことを示し
ている。Serum is separated from whole blood and subjected to purification to remove non-specific antibodies and, in particular, those produced in the animal in response to human lymphocyte composition other than multiple sclerosis antigenic components. This separation is achieved, for example, by continuous adsorption contact with lymphocyte homogenates from non-diseased patients (controls). With 4 consecutive contacts per hour, e.g.
1 ml aliquot of control lymphocyte homogenate at 7°C.
4 ml of serum sample treated with
’. The antibodies thus obtained are quite stable. Preliminary electrophoretic analysis indicates that the specific multiple sclerosis antibody appears to be microglobulin.
実施例3゜
患者のリンパ球サンプルの診断テストは、以下に例示す
る操作により行われる。用いたのは市販の免疫拡散培地
(クリニカル・サイエンス社)で、1個の中心の井戸様
くぼみと該中心の(ぼみから均一な距離を隔てて放射状
に外側に広がる6個のくぼみとを有する。ゲル培地には
0.1Nバルビドール緩衝剤中の良質寒天を用いた。Example 3 Diagnostic testing of a patient's lymphocyte sample is performed by the procedures exemplified below. A commercially available immunodiffusion medium (Clinical Science) was used, with one central well-like depression and six depressions radiating outward at uniform distances from the center depression. The gel medium used was high quality agar in 0.1N barbidol buffer.
約0.12m1のくぼみの容積が適当である。実施例2
、による約0.15m1の抗体(血清)が該中心のくぼ
みに置かれる。3個の周辺のくぼみに臨床的に診断され
た多発性硬化症患者から実施例1゜に従って得られた約
0.12m1のリンパ球均質化物が添加される。残りの
3個の細胞の各々に、テスト患者から得られた約0.1
2m1のリンパ球均質化物が添加される。培地は室温で
12ないし18時間培養せられ、それから室温で4時間
0.85%食塩水浸液中に浸漬される。培地は中心及び
周辺のくぼみの間の沈降素帯の存否が視覚的に確認され
る。中心のくぼみとテストサンプルくぼみとの間に現れ
る帯、及び中心くぼみと多発性硬化症コントロールとの
間の同一の帯は、患者の多発性硬化症を示すものである
。帯の不存在は病状のないことを示すものと看取される
。A recess volume of about 0.12 m1 is suitable. Example 2
Approximately 0.15 ml of antibody (serum) is placed in the central well. Approximately 0.12 ml of lymphocyte homogenate obtained according to Example 1° from a clinically diagnosed multiple sclerosis patient is added to three peripheral wells. Each of the remaining three cells had approximately 0.1
2ml of lymphocyte homogenate is added. The medium is incubated at room temperature for 12 to 18 hours and then submerged in a 0.85% saline soak for 4 hours at room temperature. The medium is visually checked for the presence or absence of a precipitin zone between the center and peripheral wells. A band appearing between the central depression and the test sample depression and an identical band between the central depression and the multiple sclerosis control is indicative of multiple sclerosis in the patient. The absence of a band is taken to indicate the absence of a medical condition.
実施例4゜
実施例3.の例示的操作の実施可能性は、以下の2つの
一連のテストの結果により実証される。表1はペンシル
ベニア州、エリ−地域の住民から得られたリンパ球均質
化物について行われた50の診断テストの結果に関する
。記述した如く、リンパ球は非多発性硬化症(°“正常
°°)患者、臨床的に診断された多発性硬化症患者(“
多硬”)、及び多発性硬化症以外の中枢神経系病状と臨
床的に診断された患者(“罹病゛)から採取された。免
疫拡散テストデータは、陽性の多発性硬化症の結果に対
しては“°正゛°と表示し、指標の沈降素帯がない場合
は“負”と表示する。テスト/臨床的診断の相関は“°
+゛により表示され、 −゛はかがる相関の不在を意味
する。Example 4゜Example 3. The feasibility of the exemplary operation is demonstrated by the results of the following two series of tests. Table 1 relates to the results of 50 diagnostic tests performed on lymphocyte homogenates obtained from residents of the Erie, Pennsylvania area. As described, lymphocytes are present in patients with non-multiple sclerosis (°“normal°°) and clinically diagnosed multiple sclerosis (°“
patients with clinically diagnosed central nervous system pathologies other than multiple sclerosis ("Multiple Sclerosis"). Immunodiffusion test data are displayed as “°positive゛°” for a positive multiple sclerosis result and “negative” when there is no indicator precipitin zone. Test/Clinical Diagnosis Correlation is “°
It is indicated by +゛, and -゛ means the absence of such a correlation.
サンプル テス
番号 結果
1正
2負
3正
4正
5負
6負
7正
8負
9正
10負
11負
12正
13負
表 1
ト 臨床的 テスト/臨床診断
診断 の相関
多硬 十
正常 士
多硬 +
多硬 十
正常 十
正常 士
多硬 十
罹病 十
多硬 十
多硬
正常 十
多硬 十
正常 十
罹病
多硬
多硬
多硬
多硬
多硬
罹病
正常
多硬
正常
正常
正常
正常
罹病
正常
多硬
多硬
多硬
正常
多硬
−(a)
34 正 多硬 十35
負 多硬
36 正 多硬 十37
正 多硬 十38 負 多硬
39 正 ゛ 多硬 十40
負 正常 十41 負 多硬
42 負 正常 十43
正 多硬 十44 正 多硬
十45 正 多硬 十46
正 多硬 十47 正
罹病
48 負 正常 十49
負 正常 十50 負 正常
十(a)臨床診断が後に多発性硬化症に変化した
。Sample Test Number Result 1 Positive 2 Negative 3 Positive 4 Positive 5 Negative 6 Negative 7 Positive 8 Negative 9 Positive 10 Negative 11 Negative 12 Positive 13 Negative Table 1 Multi-hardness 10 normal 10 normal Shiduo-hard 10 disease 10-hard 10-hard normal 10-hard normal Hard Normal Polyhard - (a) 34 Positive Polyhard 135
Negative multi-hard 36 positive multi-hard 137
Positive Multihard 138 Negative Multihard 39 Positive ゛ Multihard 140
Negative normal 141 Negative hard 42 Negative normal 143
Positive multihard 144 Positive multihard
145 positive hard 146
Positive multi-hard 147 positive
Morbidity 48 Negative Normal 149
Negative normal 150 Negative normal
10(a) The clinical diagnosis later changed to multiple sclerosis.
下表2はミシガン州、カラマズー地域の住民から得られ
たリンパ球均質化物につpsて実7iSiシた33の臨
床テストの結果に関する。ここでもサンプルは、正常、
多発性硬化症及び他の中枢神経系患者から得た。Table 2 below relates to the results of 33 clinical tests conducted on lymphocyte homogenates obtained from residents of the Kalamazoo, Michigan area. Again, the sample is normal,
Obtained from multiple sclerosis and other central nervous system patients.
表
臨床的
診断
正常
正常
多硬
ベル麻痺 士
糖尿病 +
SLE (a) +
罹病 十
正常 士
正常 +(b)
正常 +(c)
癲燗、鎌状赤血球士
正常 士
正常 −(b)
SLE
テスト/臨床診断
の相関
+
+
負 多硬
負 正常 十
負 多硬
負 罹病 十
正 SLE
負 罹病 十
負 正常 十
負 多硬
負 SLE +
負 a濶 十
負 SLE +
負 正常 十
負 パーキンソン+
負 罹病 士
負 パーキンソン+
負 正常 十
負 正常 十
負 正常 十
正 多硬 十
全身系顔面固定性紅斑
(b) 多発性硬化症患者の息子
(c) 多発性硬化症患者の妻
上記開示により、本発明を実施するに当たり、数多くの
修正及び変更が当業者により生じることが予測される。Table Clinical Diagnosis Normal Normal Diabetes + SLE (a) + Morbidity Normal + (b) Normal + (c) Epilepsy, sickle cell normal - (b) SLE Test/Clinical Diagnostic correlation + + Negative Multi-hard negative Normal Ten-negative Multi-hard negative Morbidity Ten-positive SLE Negative Morbidity Ten-negative Normal Ten-negative Multi-hard negative SLE + Negative a-Year Ten negative SLE + Negative Normal Ten negative Parkinson+ Negative Morbidity Parkinson+ Negative Normal 10 Negative Normal 10 Negative Normal 10 Positive Polyhard 10 Systemic facial fixed erythema (b) Son of multiple sclerosis patient (c) Wife of multiple sclerosis patient In carrying out the present invention according to the above disclosure, It is anticipated that numerous modifications and changes will occur to those skilled in the art.
先に記述したように、本発明の抗体は各種の免疫学的診
断試薬を提供するのに有用であることが期待される。免
疫拡散検定における有用性に加えて、抗体を含む血清は
凝集反応テストで使用される免疫学的に不活性な粒子(
安定化された赤血球、ラテックス・ビーズ等)を感作さ
せるために用いられる。当技術分野で良(知られた単離
及び精製技術が、螢光抗体及び放射線免疫検定臨床技術
における試薬として、ラベルが貼着された形で用いられ
た時より濃縮された状態で活性成分を確保するために抗
体調製に適用される。血清抗体からの特異的抗体の濃縮
は、同時に多発性硬化症患者の血清中に実質的により小
さい濃度で存在すると思われる抗体成分と共に、多発性
硬化症と関連性を有する特異的リンパ球抗原の単離と活
性づけを可能とすることもまた予想される。この抗原は
精製された形で、大規模、大量の抗体製造を可能とする
ためのみならず、特に“競争力のある°°タイプの免疫
検定での臨床試薬成分としてもまた有用に使用される。As described above, the antibodies of the present invention are expected to be useful in providing a variety of immunological diagnostic reagents. In addition to its usefulness in immunodiffusion assays, antibody-containing serum can be used in immunologically inert particles (
used to sensitize stabilized red blood cells, latex beads, etc.). Isolation and purification techniques well known in the art allow the active ingredient to be released in a more concentrated state when used in labeled form as a reagent in fluorescent antibody and radioimmunoassay clinical techniques. applied in antibody preparation to ensure the enrichment of specific antibodies from serum antibodies, together with antibody components that are likely to be present in substantially smaller concentrations in the serum of multiple sclerosis patients. It is also envisaged that it will be possible to isolate and activate specific lymphocyte antigens associated with It is also usefully used as a clinical reagent component, especially in competitive type immunoassays.
かかる精製された抗原は、誘発治療として一般に知られ
た治療技術による多発性硬化症の治療における治療剤と
して有用である。かかる技術によれば、疾病を引き起こ
す抗原物質の低投与量が患者の略画的全身的反応を喚起
する目的で投与される。Such purified antigens are useful as therapeutic agents in the treatment of multiple sclerosis by a therapeutic technique commonly known as induction therapy. According to such techniques, low doses of disease-causing antigenic substances are administered with the aim of evoking a generalized systemic response in the patient.
Claims (1)
と免疫学的に反応可能で、多発性硬化症患者のリンパ球
を抗原として用いることによって形成される抗体からな
る臨床試薬を構成する特異的多発性硬化症抗体を調製さ
せる接種物として好適な抗原物質であって、該抗原物質
が多発性硬化症にかかっている患者のリンパ球の均質化
物からなる抗原物質。A specific antibody that is capable of immunologically reacting with lymphocyte components that have a specific association with multiple sclerosis symptoms and that constitutes a clinical reagent consisting of antibodies formed by using lymphocytes from multiple sclerosis patients as antigens. An antigenic substance suitable as an inoculum for preparing target multiple sclerosis antibodies, the antigenic substance consisting of a homogenized product of lymphocytes of a patient suffering from multiple sclerosis.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP12548789A JPH021558A (en) | 1989-05-17 | 1989-05-17 | Method of diagnosing multiple sclerosis and substance thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP12548789A JPH021558A (en) | 1989-05-17 | 1989-05-17 | Method of diagnosing multiple sclerosis and substance thereof |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP12805581A Division JPH0230468B2 (en) | 1981-08-14 | 1981-08-14 | TAHATSUSEIKOKASHONOKENSHUTSUHOHOTOSONOBUTSUSHITSU |
Publications (1)
Publication Number | Publication Date |
---|---|
JPH021558A true JPH021558A (en) | 1990-01-05 |
Family
ID=14911308
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP12548789A Pending JPH021558A (en) | 1989-05-17 | 1989-05-17 | Method of diagnosing multiple sclerosis and substance thereof |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPH021558A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6042763A (en) * | 1996-09-20 | 2000-03-28 | Kumaoka; Shun`Ichi | Method of preparing porous ceramics provided with amorphous pore surfaces |
-
1989
- 1989-05-17 JP JP12548789A patent/JPH021558A/en active Pending
Non-Patent Citations (1)
Title |
---|
J.LAD.CLIN.MED=1979 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6042763A (en) * | 1996-09-20 | 2000-03-28 | Kumaoka; Shun`Ichi | Method of preparing porous ceramics provided with amorphous pore surfaces |
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