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WO1988008134A1 - PROCEDE ET MOYEN PERMETTANT LA DETECTION A DES FINS DE DIAGNOSTIC DE FIBRINOPEPTIDES Bbeta DERIVES D'ELASTASE - Google Patents

PROCEDE ET MOYEN PERMETTANT LA DETECTION A DES FINS DE DIAGNOSTIC DE FIBRINOPEPTIDES Bbeta DERIVES D'ELASTASE Download PDF

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Publication number
WO1988008134A1
WO1988008134A1 PCT/SE1988/000167 SE8800167W WO8808134A1 WO 1988008134 A1 WO1988008134 A1 WO 1988008134A1 SE 8800167 W SE8800167 W SE 8800167W WO 8808134 A1 WO8808134 A1 WO 8808134A1
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WO
WIPO (PCT)
Prior art keywords
elastase
fibrinopeptide
fibrinopeptides
antibody preparation
peptide
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.)
Ceased
Application number
PCT/SE1988/000167
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English (en)
Inventor
Tom Gustaf Per Saldeen
Rolf Kenth Sigvard Wallin
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Individual
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Individual
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Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of WO1988008134A1 publication Critical patent/WO1988008134A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • G01N33/6884—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids from lung
    • 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
    • G01N33/86—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood coagulating time or factors, or their receptors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/745—Assays involving non-enzymic blood coagulation factors
    • G01N2333/75—Fibrin; Fibrinogen

Definitions

  • normal value refers to the value obtained in the case of healthy persons by means of measuring methods equal to or other than the method used for the value obtained. If the value obtained and the normal value have been measured by means of methods differing inter se then if necessary the values have to be converted to values of equal scale (magni ⁇ tude) .
  • the immune response thus obtained is polyclonal, meaning that the desired antibody/ antibodies will be found in admixture with antibodies directed against other determinants of the immunogen.
  • immunosorbent purification IS purification
  • the antibodies desired will be found either in the eluate or on the adsorbent, The selection may also be based on monoclonal techniques.
  • Immunochemical methods may be classified as being either homogeneous or heterogeneous methods.
  • homo ⁇ geneous methods a labeled reactant is determined and correlated with the analyte without any physical separation of complexed reactant from the non-complexed form of the reactant.
  • heterogeneous methods the two forms of labeled reactant are separated physically from each other before the labeled reactant is assayed in one or both of the two forms.
  • the immunochemical reaction(s) contemplated will be carried out under conditions such as are commonly employed in each particular assay context.
  • the temperature thus is selected in the range of 0-40 °C, especially 15-40 °C.
  • the pH is selected from 4.5 up to 9.0, being preferably within the range of about 5-8.6.
  • Reaction solutions are buffered in a manner known per se with the aid of buffer components having a pKa within or close to the pH range in which the immune reaction to be performed will be practically independent of the pH. It is re ⁇ ommendable to add protease inhibitors and/or metal ion complexing agents like EDTA.
  • reaction mixture was then immediately diluted with 200 ,ul of buffer III.
  • the reaction mixture was then passed over a Sephadex G-10 column (1.5 x 5 cm) equilibrated and eluted with buffer II and at a flow rate of 0.25 ml/min. Fractions of 0.5 ml were collected. The protein-peptide peak contained most of the radioactivity (90 %) .
  • Fractions containing the tracer were pooled, diluted with 4 volumes of buffer III and dispensed in 0.2 ml aliquots which were stored frozen at -25 C until used. The tracer is stable for at least 4 mc without loss of any of its immune reactivity.
  • B ⁇ 30-43 RIA Dilutions of standard, test samples, antiserum and tracer were made in buffer IV. Each assay tube contained 100 .ul of standard concentration of B ⁇ d 30-43 or test sample (undiluted plasma, urine etc) + 50 ,ul of tracer + 100 ,ul of antiserum in a dilution sufficient to bind 35 % to 45 % of the total bindable tracer. After each step the tubes were shaken thoroughly. After a 16 h incubation period at +4 C, free tracer and tracer bound to antibody were separated by adding 500 ,ul of dextran-coated active carbon (consisting of 1 % carbon and 0.1 % Dextran-T 70) (final cone.) at 0 C.
  • the tubes were shaken thoroughly and left on ice for 5 min. They were then centrifuged for 10 min at +4 C and 1 500 g 600 ,ul of the supernatants were transferred to new tubes, and radioactivity was counted on a gamma counter.
  • Fibrinogen Its concentration in citrated plasma was deter ⁇ mined by the method of Nilsson and Olow (21) .
  • Bp 30-43 peptide in plasma 0.45 ml of (1) citrate-, (2) heparin + trasolyl- and (3) EDTA-plasma was incubated each by itself with 0.05 ml of B 30-43 peptide (1 ,umol/L) . The incubations were performed at 0 C, +22 C and +37 C.
  • the diffusates contained all of the immunological activities.
  • the desired peptide could be isolated from the diffusates, by means of a combination of gel chromatography on Bio Gel P6 ® in 0.1 M ammoniumacetate, pH 6.2 and HPLC on Mono Q in 0.02 M ethanolamine, pH 9.5.
  • the active material was lyophilized and amino acid analyzed on a Durrum D-500 analyser. The active fractions obtained with digest from fibrin or fibrinogen were the same both in gel chromatography and HPLC.
  • Cross reactivity of the antibody preparation Cross reac ⁇ tivities of peptides B ⁇ 1-42, B> 15-42, B ⁇ » 1-118 and peptide ]_A 30-43 NH 2 with the anti-(B 30-43)-antibody were determined. Varying concentrations of fibrinogen were also studied. The results are summarized in Tables I and II.
  • the invention has been applied to a clinical material. What we found was that elevated values of elastase induced Bl» fibrinopeptides can be demonstrated in i.a. inflammatory conditions, for example in cases of som diseases of the lungs (pulmonary congestion, pulmonary embolism) and diseases of the kidneys (probably associated with glomerular lesions) . Very high levels have been demonstrated in particular in cases of ARDS and septic patients.
  • Bilezikikian S.B. et al. : J. Clin. Invest. 53: 438-45, 1975.

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Hematology (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Urology & Nephrology (AREA)
  • Food Science & Technology (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Biotechnology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Microbiology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Peptides Or Proteins (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

Procédé permettant le diagnostic in vitro de maladies associées à la fibrin(ogèn)olyse et/ou l'activité pathologique d'élastase, caractérisé en ce qu'un échantillon prélevé sur un patient et contenant des fibrinopeptides est soumis à la quantification d'au moins un fibrinopeptide Bbeta 14(U2) - 45(U3) dérivé d'élastase. La valeur ainsi obtenue est comparée à une valeur normale d'individus en bonne santé, et si la valeur obtenue est supérieure à la valeur normale, le patient sur lequel on a prélevé l'échantillon est classé comme étant malade. Le procédé d'analyse offre une manière de démontrer la présence d'activité sans élastase dans des échantillons prélevés sur des patients. En outre, de nouvelles préparations ainsi que de nouvelles préparations de fibrinopeptides Bbeta 14(U2) - 45(U3) dérivés d'élastase pouvant être employées dans ledit procédé sont décrites.
PCT/SE1988/000167 1987-04-06 1988-04-05 PROCEDE ET MOYEN PERMETTANT LA DETECTION A DES FINS DE DIAGNOSTIC DE FIBRINOPEPTIDES Bbeta DERIVES D'ELASTASE Ceased WO1988008134A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE8701437A SE8701437L (sv) 1987-04-06 1987-04-06 Diagnostiskt foerfarande in vitro samt medel som kan utnyttjas vid foerfarandet
SE8701437-9 1987-04-06

Publications (1)

Publication Number Publication Date
WO1988008134A1 true WO1988008134A1 (fr) 1988-10-20

Family

ID=20368117

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/SE1988/000167 Ceased WO1988008134A1 (fr) 1987-04-06 1988-04-05 PROCEDE ET MOYEN PERMETTANT LA DETECTION A DES FINS DE DIAGNOSTIC DE FIBRINOPEPTIDES Bbeta DERIVES D'ELASTASE

Country Status (5)

Country Link
EP (1) EP0353242A1 (fr)
JP (1) JPH02503033A (fr)
AU (1) AU1596188A (fr)
SE (1) SE8701437L (fr)
WO (1) WO1988008134A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0345906A3 (en) * 1988-06-10 1990-11-22 Merck & Co. Inc. Unique elastase induced fibrinogen cleavage site antigens
US6124107A (en) * 1988-06-10 2000-09-26 Merck & Co., Inc. Assay for marker of human polymorphonuclear leukocyte elastase activity
RU2195660C1 (ru) * 2001-06-07 2002-12-27 Савина Лидия Васильевна Способ диагностики гиперэластаземии
WO2006101436A1 (fr) * 2005-03-22 2006-09-28 Astrazeneca Ab Empreinte peptidique obtenue a partir de la degradation de l'elastine par hne
CN108473559A (zh) * 2015-11-10 2018-08-31 威特拉公司 特异性结合脂多糖的抗体分子-药物共轭物及其应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0151239A2 (fr) * 1983-11-14 1985-08-14 New York Blood Center, Inc. Anticorps monoclonaux spécifiques de fragments dérivés in vivo de fibrinogène
EP0152612A2 (fr) * 1984-01-09 1985-08-28 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Détermination de fibrine avec anticorps spécifiques à fibrine

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0151239A2 (fr) * 1983-11-14 1985-08-14 New York Blood Center, Inc. Anticorps monoclonaux spécifiques de fragments dérivés in vivo de fibrinogène
EP0152612A2 (fr) * 1984-01-09 1985-08-28 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Détermination de fibrine avec anticorps spécifiques à fibrine

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
Blood, Vol. 67, pages 1014-1022, published April 1986 (J.I. WEITZ et al.) "Development of a Radioimmunoassay for the Fibrinogen-derived Peptide B beta 1-42". *
Blood, Vol. 688 No. 2, pages 437-441, published August 1986 (KOPPERT P. W. et al.) "Production and Characterization of a Monoclonal Antibody Reactive with a Specific Neoantigenic Determinant (comprising B beta 54-118) in Degradaation Products of Fibrin and of Fibrinogen". *
Blunt, Vol. 53, pages 1-9, published 1986 (PLOW E. F.) "The Contribution of Leukocyte Proteases to Fibrinolysis". *
Blut, Vol. 53, pages 39-48, published July 1986, (ECKHART T.) "Fibrinogen Proteolysis in Acute Myelogenous Leukemia (AML)". *
Trombosis Research Vol. 25, pages 277-291, published 1982 (KUDRYK B. et al.) "Measurement in Human Blood of Fibrinogen/Fibrin Fragments Containing the B beta 15-42 Sequence". *
Trombosis Research Vol. 31, pages 719-728, published 1983 (STERRENBERG L. et al.) "Granulocyte Enzyme Mediated Degradation of Human Fibrinogen in Plasma in Vitro", see in particular page 726, last paragraph. *
Trombosis Research Vol. 37, pages 85-89, published 1985 (SALDEEN K. et al.) "Effect of a Fibrinogen-derived Vasoactive Peptide on Polymorphonuclear Leukocyte Emigration". *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0345906A3 (en) * 1988-06-10 1990-11-22 Merck & Co. Inc. Unique elastase induced fibrinogen cleavage site antigens
US6124107A (en) * 1988-06-10 2000-09-26 Merck & Co., Inc. Assay for marker of human polymorphonuclear leukocyte elastase activity
RU2195660C1 (ru) * 2001-06-07 2002-12-27 Савина Лидия Васильевна Способ диагностики гиперэластаземии
WO2006101436A1 (fr) * 2005-03-22 2006-09-28 Astrazeneca Ab Empreinte peptidique obtenue a partir de la degradation de l'elastine par hne
CN108473559A (zh) * 2015-11-10 2018-08-31 威特拉公司 特异性结合脂多糖的抗体分子-药物共轭物及其应用

Also Published As

Publication number Publication date
SE8701437L (sv) 1988-10-07
EP0353242A1 (fr) 1990-02-07
SE8701437D0 (sv) 1987-04-06
AU1596188A (en) 1988-11-04
JPH02503033A (ja) 1990-09-20

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