[go: up one dir, main page]

WO2002009793A1 - Dispositif de traitement de maladies du systeme immunitaire - Google Patents

Dispositif de traitement de maladies du systeme immunitaire Download PDF

Info

Publication number
WO2002009793A1
WO2002009793A1 PCT/DE2001/002884 DE0102884W WO0209793A1 WO 2002009793 A1 WO2002009793 A1 WO 2002009793A1 DE 0102884 W DE0102884 W DE 0102884W WO 0209793 A1 WO0209793 A1 WO 0209793A1
Authority
WO
WIPO (PCT)
Prior art keywords
antigens
antigen
immune
blood
anchor
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/DE2001/002884
Other languages
German (de)
English (en)
Other versions
WO2002009793A8 (fr
Inventor
Torsten Matthias
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Aeskulab Diagnostika
Original Assignee
Aeskulab Diagnostika
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Aeskulab Diagnostika filed Critical Aeskulab Diagnostika
Priority to DE10193004T priority Critical patent/DE10193004D2/de
Priority to AU2001278407A priority patent/AU2001278407A1/en
Publication of WO2002009793A1 publication Critical patent/WO2002009793A1/fr
Publication of WO2002009793A8 publication Critical patent/WO2002009793A8/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K17/00—Carrier-bound or immobilised peptides; Preparation thereof
    • C07K17/02—Peptides being immobilised on, or in, an organic carrier
    • C07K17/06—Peptides being immobilised on, or in, an organic carrier attached to the carrier via a bridging agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/3472—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate
    • A61M1/3486—Biological, chemical treatment, e.g. chemical precipitation; treatment by absorbents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3679—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by absorption
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/04—Liquids
    • A61M2202/0413—Blood
    • A61M2202/0415—Plasma
    • A61M2202/0417—Immunoglobulin

Definitions

  • the invention relates to a device for the treatment of immune diseases and the use of substances to which autoantibodies bind, such as e.g. of antigens, for the production of an agent for the treatment of immune diseases and a kit containing such agents.
  • the immune system's task is to ward off attacks on the organism and to fight foreign objects that have penetrated. It must not only differentiate between dangerous and harmless foreign bodies, but also be able to recognize the body's own substances. Dangerous attacks on the organism are, for example, the penetration of microorganisms, whereas the penetration of food antigens into the bloodstream when eating or the inhalation of bee pollen is harmless. In the defense, the destruction of foreign cell material is e.g. in the case of a parasitic infestation, as desirable as the destruction of the body's own malignant cells, whereas the attack on healthy body's own tissue, such as in autoimmune diseases, is undesirable. This means that the immune system has regulatory processes that prevent destructive self-reactivity. This ability is called "tolerance". If this tolerance is lost, immune diseases develop.
  • Immune diseases based on an unwanted immune response or response are playing an increasingly common role. For example, it is known that the frequency of immune reactions, which are directed against harmless foreign bodies such as grass pollen and animal hair, but also against food components, increases and leads to sensitization and thus to an allergy of an organism, which lead to serious diseases if sufficiently exposed.
  • Another Re unwanted immune disease is the rejection reaction of the host versus graft type or in organ transplants, which are recognized as foreign by the body's immune system and are attacked and destroyed accordingly like a bacterium.
  • autoimmune diseases Another important undesirable malfunction of the immune system are the so-called autoimmune diseases.
  • the body's own tissue or body's own cell substances or cells are wrongly regarded as foreign and are combated accordingly.
  • the development of such autoimmune diseases is diverse. They can be triggered, for example, by intracellular substances entering the bloodstream as a result of injuries. Since these substances were previously hidden or enclosed in a cell, their antigens or epitopes could not be known to the immune system and could not be recognized as the body's own. They are therefore considered foreign to the body. For this reason, they are able to trigger an immune response.
  • An example of such an autoimmune disease is sympathetic ophthalmia, in which a traumatic event releases an endogenous substance or an antigen that is normally enclosed in the eye.
  • autoimmune diseases Another cause for the development of autoimmune diseases is, for example, that antigens recognized by the immune system as the body's own, so-called “own” antigens, are changed by chemical, physical or biological effects and are therefore no longer regarded as “own” but as “foreign” In this way, they become immunogenic and can trigger an immune attack on your own body. It is known, for example, that some chemicals bind to the body's own proteins and thus make them immunogenic, as can be seen, for example, in contact dermatitis. In so-called sun allergy, skin proteins are changed by ultraviolet light so that they are no longer recognized by the immune system and trigger an immune response, making the patient allergic.
  • immunosuppressive substances such as anti-inflammatory glucocorticoids, e.g. B. cortisone, non-steroidal anti-inflammatory drugs (NSAIDs), which intervene in the prostaglandin metabolism, immunosuppressive cytochins such as interleukin 10, antimetabolites such as metotrexate, cytostatics such as cyclophosphamide or inhibitors of inflammation-stimulating cytokines such as cyclosporin A or mycophenolinol, also mycophenolunol.
  • NSAIDs non-steroidal anti-inflammatory drugs
  • WO-97/14964 describes a procedure according to which the immune complexes circulating in it are isolated from the patient's blood using conventional methods and these are separated into their antigen and antibody components by methods known per se. The antigens and antibodies thus obtained are then covalently coupled individually or as a mixture to suitable carriers and used as an immune absorber for precisely those patients from whom the immune complexes have been isolated. In this way, specifically acting immune absorbers for patients suffering from autoimmune diseases are to be produced.
  • the aim of the invention is therefore to overcome the disadvantage of the prior art and to provide a means and a device with which undesirable immune diseases can be treated without completely suppressing the patient's immune system.
  • the agent should be quick and inexpensive to manufacture, easy to store and quick to assemble, ready to use, and moreover, it should also be quickly adaptable to the patient's immunological needs on site.
  • the invention is also intended to treat particularly fatal immune diseases such as sprue, celiac disease, Goodpasture syndrome, myasthenia gravis, Wegner's granulomatosis, asthma and heart diseases, IgE-mediated allergies, pemphigus vulgaris, autoimmune hepatitis, Rasmussen's encephalitis, Schnitz / or enable chronic urticaria.
  • the invention also aims to preventively prevent the development of immune diseases and / or to reduce or to avoid the consequential damage of such diseases.
  • the invention thus relates to a device for the treatment of immune diseases which has substances immobilized on a solid phase which bind gressive immunoglobulins, preferably selectively.
  • substances are, in particular, antigens which trigger the immune disease.
  • the blood or its aqueous constituents are washed around the carrier, the pathogenic immunoglobulins being removed from the blood.
  • Those immunocompetent cells and precursor cells which form the aggressive antibodies, in particular B cells are preferably also removed.
  • This effect on which the invention is based is all the more surprising because it was to be expected that the exposure of antigens to the immune system of the blood should increase the immune response, ie the formation and post-production of immunoglobulins directed against it (so-called booster Effect).
  • the aggressive immune response can be reduced or even down-regulated in a targeted manner if the undesired aggressive antibodies or immunoglobulins are selectively removed.
  • This selective removal is preferably achieved according to the invention by means of an antigen directed against the aggressive antibodies, against which the aggressive immunoglobulin is directed.
  • these are in particular the foreign HLA or MHC antigens.
  • these are the antigens which trigger autoimmunity.
  • the antigens bound in the device according to the invention are immobilized on a solid phase by methods known to the person skilled in the art.
  • the immunoglobulin-binding substances can be bound to the solid phase either directly or indirectly. They are preferably connected to one another by means of a non-covalent coupling consisting of at least 2 complementary coupling members.
  • the coupling member attached to the immobilized agent is referred to as the anchor and the complementary coupling member bound to the solid phase is referred to as the counter anchor. Examples include only immobilization using cyanogen bromide or fixation using glutaraldehyde (direct binding), and biotinylation and the formation of avidin or streptavidin complexes.
  • the antigens are bound to the surface or solid phase by means of a spacer, ie an arm or spacer.
  • a spacer ie an arm or spacer.
  • preferred spacers allow a distance of the antigen from the solid surface or the solid phase of preferably at least 5 A, in particular at least 10 ⁇ , with at least 15 A and in particular at least 20 ⁇ being particularly preferred.
  • Spacer arms which allow a distance of at least 28 A, in particular at least 30 A, are very particularly preferred.
  • the spacers are expediently constructed from a long carbon chain, but they are preferably constructed from repetitive units of smaller hydrocarbon chains, which in particular have heteroatoms. Preferred repetitive units are in particular C 2 -C 8 units, with C to C 6 being particularly preferred.
  • the individual units are preferably linked to one another via the heteroatoms.
  • Preferred heteroatoms are nitrogen, oxygen and sulfur atoms.
  • the repetitive units are preferably connected to one another via amino acid functions.
  • the spacer arms preferably have different reactive groups at their two ends, one group of which reacts with the antigen to be bound, ie to be immobilized, and the other binds to the surface and, where appropriate, reacts there with it.
  • Preferred functional groups which react with the antigens are, in particular, N-hydroxysuccinimide, sulfo-N-hydroxysuccinimide groups which react, for example, with a primary amine to form an amide group with the antigen or maleimide groups, for example with a free sulfhydryl group of an antigen to form a thioether bridge.
  • haloacetyl especially an iodoacetyl group, which also reacts with sulfhydryl to form a thioether bridge.
  • Other important reactive reagents are, for example, hydrazide groups, which react with an oxidized carbohydrate group, for example an aldehyde group to form a hydrazone bond, further important groups are, for example, photoactivatable azido groups, for example aromatic azido groups, which contain nucleic acids and protein carbohydrates react with a primary amine to form a ring expansion.
  • amino groups are used which react to form a free carboxylic acid or carboxy group to form an amido bond.
  • Many such reagents are commercially available. In the case of the aforementioned functional reagents, the reagents containing N-hydroxysuccinimide and the maleimide containing reagents and the amino groups and the photoactivatable azido groups are preferred.
  • the spacer arm has an anchor group which, in particular non-covalently, couples with a counter anchor immobilized on the solid surface.
  • the anchor on the spacer arm is preferably arranged at the point opposite the binding point of the spacer with the antigen.
  • Anchors preferred according to the invention are biotin, thioredoxin, and / or polyhistidine tags, in particular those with 4 to 6 histidine residues adjacent to one another.
  • Preferred counter anchors are avidin and in particular streptavidin as counter anchor to biotin, a chelato-immobilized metal ion, in particular nickel and / or cobalt, expediently as counter anchor to polyhistidine tags, and an antibody directed against the anchor.
  • Such antibodies are easy to produce and in some cases also as monoclonal antibodies e.g. from ACC-2207 (antipentahistidyl antibody) commercially available from Quiagen.
  • Such anchors and spacers containing reactive groups can be readily produced by a person skilled in the art and are also commercially available, for example.
  • Pierce, Rockford, IL, 61105, USA sells them under the name EZ-Link TM and under the name Sulfo-LC-SPDP, LC-SPDP and SPDP. Fissile crosslinking reagents are also commercially available under this name.
  • the procedure according to the invention makes it possible to provide the surface of the solid phase with the counter-anchor first, even under reaction-hostile protein and nuclein conditions. Since it is not necessary to pay attention to biologically compatible reaction conditions, very high densities of counter anchors can also be achieved on the surface of the solid phase, as was previously not possible with the direct immobilization of antigens. After completion of the solid phase thus provided with the counter anchor, it can be loaded with the antigen under physiological conditions using its anchor day. In this way it is possible to achieve loading densities of> 0.01 pmol / cm 2 > 0.1 pmol / cm 2 and in particular> 1 pmol / cm 2 . Even densities of> 5 pmol / cm 2 can be easily achieved.
  • densities of> 10 nmol / cm 3 , in particular> 20 nmol / cm 3 and beyond, can be produced, for example, in the case of beads with a diameter of 40-90 ⁇ m.
  • streptavidin The biotinylin system, which can bind up to four biotinylin anchors, enables exceptionally high loading densities. In this way, small, highly effective immune absorbers can be produced.
  • the procedure according to the invention also makes it possible to produce the required immune absorbers on site, ie. H. For example, in a clinic or other therapy center to manufacture yourself if necessary. Since it is no longer necessary to store the entire required devices, but only the non-specific solid phases provided with the anchor, i. H. Columns, dialysis tubes, hollow fibers etc. as well as the respective antigens provided with the spacer arm and anchor, it is possible, if necessary, to immediately produce a specific immune absorber for the particular disease required by producing a solution of the antigen provided with spacer and anchor and in contact with the surface of the solid phase. Since the respective antigens can be stored for a long time, for example in the lyophilized state, no large, voluminous storage is necessary in order to provide a large number of absorbers for various diseases.
  • Another advantage is that it is designed by providing a general prefabricated absorber that can be quickly prepared for a variety of different diseases.
  • the procedure according to the invention thus makes it possible to bind the antigens in their native physiological conformation without being sterically hindered by the immobilization on the surface, as a result of which almost all epitopes of the antigen are accessible to the antibodies to be removed or to the cells producing them .
  • the anchor systems used according to the invention bind the antigen to the absorber with a high affinity, thereby preventing detachment or bleeding.
  • the binding of the antigen according to the invention to the column enables washing of the bound autoagressive substances after use, for. B. by using high salt solutions and / or changes in pH. In this way, the respective immune absorbers can be used multiple times, i. H. be recycled.
  • carrier materials are all substances to which antigens or components thereof can be bound.
  • Usual carrier materials to which the antigens are bound are also known from the manufacture of diagnostic test kits and for the manufacture of dialysis tubes. In principle, they are not subject to any restrictions, they may only be non-toxic and not themselves be allergic.
  • Suitable carrier materials are, for example, silica gels as used for packed columns, latex particles, in particular non-allergenic latex particles, glass beads, gel matrices and hollow body matrices such as filter materials and dialysis tubes.
  • particles made of polystyrenes, polyvinyl alcohols, Sepharose etc. can also be used.
  • the solid phases preferably have a large surface area around which the blood serum or an aqueous solution of components thereof flows, so that a maximum contact area between antigens and the immunoglobulins circulating in the blood is created.
  • antigens means all substances against which aggressive antibodies are directed. These are usually proteins, nucleic acids, and complexes of these two, possibly also with membrane components. This includes not only the complete antigens, but also parts or fragments of them that have bindable epitopes, such as peptides, oligopeptides and oligonucleotides, which can possibly also be produced artificially.
  • Preferred antigens to be immobilized according to the invention are double-stranded DNA, single-stranded DNA, nucleosomes, centromeres (kinetochore antigen), Jo-1 (histidyl synthetase), SCL-70 (topoisomerase I), PCNA (proliferating cell nuclear antigen) , SS-B / La, SS-A (Ro), U1-RNP, SN antigen (small nuclear antigen), histones, PR3 (proteinase 3), F c fragment of immunoglobulin, citrulline, phospholipids such as cardiolipin, ANA , ribosomal protein, RA 33, PM-Scl, ANCA, GBM (basement membrane of the kidney glomeruli), acetylcholine receptors, insulin receptors, antibody-sensitized platelets.
  • centromeres kinetochore antigen
  • Jo-1 histidyl synthetase
  • antigens are, for example, antigens of sympathetic ophthalmia and B5 for Behcet's disease, B 27 for ankylosing spondylitis, Reiter's disease, and acute anterior uveitis, B 35 for subacute thyroiditis, Cw 6 for psoriasis vulgaris, DR 3 and possibly DR 4 for dermatitis herpetiformis, celiac disease, and Graves' disease, type I diabetes mellitus, myasthenia gravis, systemic lupus erythematosus (SLE), idiopathic membranous nephropathy; DR 2 for narcolepsy and multiple sclerosis, DR 4 for rheumatoid arthritis, and DR 5 for Hashimoto's thyroiditis and pernicious anemia and DRw8 for juvenile chronic arthritis; as well as the class of the spectrins, in particular ⁇ - and ⁇ -fodrin.
  • the procedure according to the invention it is also possible to immobilize the respective antigens which trigger the autoaggressive reaction. It has been shown that these do not occur in the serum, particularly in the case of particularly fatal diseases.
  • the respective main antigens such as the C-terminal end of the ⁇ -3 chain of the Isolate type IV collagen of the glomerular basement membrane separately and provide it with the appropriate spacer arm having an anchor. As already mentioned, this can also be done recombinantly.
  • membrane-bound antigens of this type into phospholipid vesicle membranes and then to bind them to the surface of the absorber in the manner described above.
  • Such important antigens that are identical for most affected patients are in particular transglutaminase and gliadin for celiac disease or sprue, and the aforementioned III collagen, in particular its C-terminal end for Goodpasture syndrome.
  • Further special antigens to be used according to the invention are, for example, the acetylcholine receptor and the ⁇ -2-adrenergic receptor for the treatment of myasthenia gravis and the proteinase 3 which occurs in the ⁇ -granules of the neutrophilic granulocytes for the treatment of Wegner's granulomatosis.
  • ⁇ -adrenergic receptors in particular ⁇ 1 and ⁇ 2 receptors
  • IgE receptors can be used according to the invention as antigens for severe cases of IgE-mediated allergies.
  • Another antigen of the desmosome in particular desmocholine, which is special and not present in the serum and which is used for the treatment of pemphigus vulgaris.
  • Further special antigens to be used according to the invention are the asialoglycoprotein receptor for autoimmune hepatis, the glutamate receptor for Rasmussen encephalitis, the interleukin-1- ⁇ receptor for Schnitzler's syndrome, and the IgE receptor for chronic urticaria.
  • the autoantibodies involved in the formation of tissue-damaging immune complexes are removed, but also the removal of such autoantibodies which can cause tissue damage per se.
  • the application thus affects more diseases and can also be used as a preventive measure that removes the autoantibodies before the formation of immune complexes.
  • not only real autoantibodies, but also other pathogenic antibodies can be removed, such as B. Allergy Antibodies.
  • Such a device according to the invention is now connected to a blood collection point arranged on a patient via a feed line analogous to dialysis. the blood being drawn from this and passed over the device according to the invention.
  • the blood being drawn from this and passed over the device according to the invention.
  • the immunoglobulins which cause illness, but also these producing cells and precursors thereof are preferably bound to the immobilized antigens and the blood is freed of them.
  • this "liberated” or “cleaned” blood is returned to the patient via a drain by means of a blood return point.
  • the removal, filtration and recycling are preferably carried out continuously.
  • Blood sampling or blood return point are devices such as are known, for example, from dialysis or from blood donation.
  • the device according to the invention it is not only possible to remove immunoglobulins, but it is also possible to selectively remove immunocompetent cells, which are responsible for the excessive immune reaction, without depriving the patient of his remaining protection, which is necessary for sufficient immunity to pathogens ,
  • immunocompetent cells which are responsible for the excessive immune reaction
  • IMS magnet
  • Such particles are available, for example, from Bekton-Dickensen under the name Dynabeads.
  • Another possibility is, for example, to provide the antigens with a cytometrically recognizable marker, in particular fluorescent marker, and then to remove corresponding unwanted immune cells by means of flow cytometry.
  • a cytometrically recognizable marker in particular fluorescent marker
  • the invention thus also relates to a therapy kit which device according to the invention or the agent produced according to the invention together with an immunosuppressant.
  • the invention it is also possible to connect a plurality of devices having different antigens in series and to remove a number of different aggressive immunoglobulins in this way. This can be done, for example, by filling the antigens immobilized on particles in columns and connecting several columns coated with different antigens in series. In principle, this is also possible with appropriate dialysis tubes or with filter matrices or hollow fibers.
  • the diseases to be treated with the device according to the invention are in particular all allergic and autoimmune diseases in which antibodies play a role relevant to the disease, i.e. have a pathogenic effect.
  • diseases include, in particular, systemic lupus ery-thematodes (SLE), Sjogren's syndrome, scleroderma, polymyositis, dermatomyositis and mixed collagen disease (MCTD) as well as rheumatoid arthritis, primary vasculitis, and antiphospholipid syndrome, gypsum , Polychondritis, uveitis, Behcet's disease and especially the Goodpasture syndrome (AK against renal basal membrane), as well as myasthenia (myasthenia gravis), multiple sclerosis, cardiomyopathy, heart failure and pemphigus vulgaris.
  • SLE systemic lupus ery-thematodes
  • MCTD mixed collagen disease
  • gypsum Polychondritis, uveitis, Be
  • purified proteinase 3 (PR 3) is concentrated to about 10 mg / ml by means of ultrafiltration over a 10 kDa membrane (made of polyether sulfone or regenerated cellulose).
  • concentration is estimated by means of the absorbance at 280 nm by dilution of 1: 100 in PBS, using pure PBS as the basic value.
  • the measured extinction value is to be multiplied by 100, a value of 1 corresponding to approximately 1 mg / l protein.
  • the solution thus concentrated is buffered on a 5 ml hightrap desalination column (Pharmacia, Sweden) in PBS, with a maximum of 1 ml sample per run being charged.
  • the protein solution thus obtained is contained with a 10 mg / ml
  • the reagent is added to the protein in about 4-fold excess and incubated on ice for two hours.
  • Unreacted reagent is separated by means of gel filtration, as previously described for the buffering.
  • the biotinylated antigen obtained in this way can be stored with 0.1% sodium azide at 4 ° C. and soon processed further or lyophilized for longer storage.
  • the PR3 antigen thus obtained which was provided with a biotin anchor, was placed on a column containing polymethacrylate beads, which are coated with monomeric avidin.
  • avidin-coated polymethacrylate beads are available, for example, under the name Softlink TM from Promega, Wl, USA.
  • the material is incubated for 15 minutes at room temperature with 5 mM biotin in order to suppress non-specific bindings.
  • the column was eluted with 10% acetic acid and then with PBS.
  • the biotinylated PR3 antigen was then loaded onto the column and then washed.
  • the column thus obtained was charged with 500 ml of plasma from a Wegner patient.
  • the antibody titer of the plasma showed an OD of 1.9 in an anti-PR3 ELISA test from Aesku.lab Diagnostika before application to the column. After passing through this column (10 ml column) it still showed an OD of 0.15. This means that with a single pass on such a tiny column, 92.1% of the disease-causing agent has already been removed.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Vascular Medicine (AREA)
  • Molecular Biology (AREA)
  • Public Health (AREA)
  • Hematology (AREA)
  • Medicinal Chemistry (AREA)
  • Anesthesiology (AREA)
  • Immunology (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cell Biology (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Cardiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Transplantation (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • External Artificial Organs (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne un dispositif de traitement de maladies du système immunitaire comprenant un conduit d'alimentation destiné au sang et/ou aux constituants sanguins aqueux et pouvant être raccordé à un point de prélèvement du sang placé dans un organisme humain, un conduit de dérivation pouvant être raccordé à un point de renvoi du sang placé dans l'organisme humain et un support situé entre le conduit d'alimentation et le conduit de dérivation et présentant une surface. Le dispositif est caractérisé en ce que la surface du support présente des antigènes immobilisés qui lient de façon sélective des immunglobulines agressives. Les antigènes immobilisés qui, de préférence, ne sont pas présents dans le sérum, sont liés au support notamment à l'aide d'une fixation par liaison non covalente.
PCT/DE2001/002884 2000-07-27 2001-07-27 Dispositif de traitement de maladies du systeme immunitaire Ceased WO2002009793A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
DE10193004T DE10193004D2 (de) 2000-07-27 2001-07-27 Vorrichtung zur Behandlung von Immunerkrankungen
AU2001278407A AU2001278407A1 (en) 2000-07-27 2001-07-27 Device for treating immune diseases

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10036742A DE10036742A1 (de) 2000-07-27 2000-07-27 Vorrichtung zur Behandlung von Immunerkrankungen
DE10036742.9 2000-07-27

Publications (2)

Publication Number Publication Date
WO2002009793A1 true WO2002009793A1 (fr) 2002-02-07
WO2002009793A8 WO2002009793A8 (fr) 2002-04-18

Family

ID=7650487

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE2001/002884 Ceased WO2002009793A1 (fr) 2000-07-27 2001-07-27 Dispositif de traitement de maladies du systeme immunitaire

Country Status (3)

Country Link
AU (1) AU2001278407A1 (fr)
DE (2) DE10036742A1 (fr)
WO (1) WO2002009793A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2842746A1 (fr) * 2002-07-26 2004-01-30 Univ Nancy 1 Henri Poincare Colonne d'immunoaffinite pour epuration d'anticorps comportant des microparticules polymeres encapsulant des antigenes associes a des phospholipides

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0103184A2 (fr) * 1982-08-12 1984-03-21 Kanegafuchi Chemical Industry Co., Ltd. Activation de terpolymères biocompatibles par des agents biologiques dont les compléments à fixer sont des effecteurs pathologiques
US4705628A (en) * 1985-04-09 1987-11-10 Terumo Kabushiki Kaisha Immunoglobulin adsorbent and adsorption apparatus
WO1993003735A1 (fr) * 1991-08-23 1993-03-04 Alberta Research Council Procedes et compositions d'attenuation de rejet de xenogrephe induit par les anticorps chez les receveurs humains
US5871649A (en) * 1996-06-20 1999-02-16 Baxter International Inc. Affinity membrane system and method of using same
WO2000041718A1 (fr) * 1999-01-11 2000-07-20 Baxter International, Inc. Methode et dispositif permettant d'extraire selectivement des anticorps xenoreactifs du sang, du serum ou du plasma

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4865841A (en) * 1987-10-23 1989-09-12 Imre Corporation Methods and compositions for transient elimination of humoral immune antibodies
DE3887750T2 (de) * 1987-11-20 1994-09-15 Creative Biomolecules Inc Selektive entfernung von immunkomplexen.
DE19538641C2 (de) * 1995-10-05 2000-09-21 Privates Inst Bioserv Gmbh Patientenspezifische Immunadsorber für die extrakorporale Apherese und Verfahren für deren Herstellung
AU736826B2 (en) * 1998-01-20 2001-08-02 Mitra Medical Technology Ab An apparatus for use in connection with removal of elements, especially exogenous antibodies, from blood or plasma

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0103184A2 (fr) * 1982-08-12 1984-03-21 Kanegafuchi Chemical Industry Co., Ltd. Activation de terpolymères biocompatibles par des agents biologiques dont les compléments à fixer sont des effecteurs pathologiques
US4705628A (en) * 1985-04-09 1987-11-10 Terumo Kabushiki Kaisha Immunoglobulin adsorbent and adsorption apparatus
WO1993003735A1 (fr) * 1991-08-23 1993-03-04 Alberta Research Council Procedes et compositions d'attenuation de rejet de xenogrephe induit par les anticorps chez les receveurs humains
US5871649A (en) * 1996-06-20 1999-02-16 Baxter International Inc. Affinity membrane system and method of using same
WO2000041718A1 (fr) * 1999-01-11 2000-07-20 Baxter International, Inc. Methode et dispositif permettant d'extraire selectivement des anticorps xenoreactifs du sang, du serum ou du plasma

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BOUTAUD A A ET AL: "GOODPASTURE SYNDROME: SELECTIVE REMOVAL OF ANTI-ALPHA3(IV) COLLAGENAUTOANTIBODIES A POTENTIAL THERAPEUTIC ALTERNATIVE TO PLASMAPHERESIS", EXPERIMENTAL NEPHROLOGY, KARGER, DE, vol. 4, no. 4, 1996, pages 205 - 212, XP001029514, ISSN: 1018-7782 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2842746A1 (fr) * 2002-07-26 2004-01-30 Univ Nancy 1 Henri Poincare Colonne d'immunoaffinite pour epuration d'anticorps comportant des microparticules polymeres encapsulant des antigenes associes a des phospholipides

Also Published As

Publication number Publication date
DE10193004D2 (de) 2002-10-31
DE10036742A1 (de) 2002-02-21
AU2001278407A1 (en) 2002-02-13
WO2002009793A8 (fr) 2002-04-18

Similar Documents

Publication Publication Date Title
DE69531290T2 (de) Antigen-besierende heteropolymere zur behandlung von autoimmunkrankheiten mittels diesen
DE69222303T2 (de) Kationisierte antikörper gegen intrazelluläre eiweisse
DE68913402T2 (de) Antikörper mit hoher Affinität für Methamphetamine sowie geeignetes Immunogen für seine Herstellung.
DE60014239T2 (de) Reinigungsverfahren von verbindeten Ig Fraktionen mit immunomodulierender Aktivität
EP1163004B1 (fr) Immuno-adsorbants pour le traitement de la septicemie
CH644521A5 (de) Therapeutisches immunosuppressives mittel und verfahren zu dessen herstellung.
EP1663347B1 (fr) Dispositif de prélèvement par aphérèse
DE4244715A1 (de) Verfahren zur Herstellung individuum-spezifischer, gegen Tumor antigene gerichtete monoklonale Antikörper
EP1570272A2 (fr) Identification d'autoanticorps agonistes
DE2732437B2 (de) Wasserunlösliches Haptoglobinpräparat und Verfahren zu seiner Herstellung
WO2002009793A1 (fr) Dispositif de traitement de maladies du systeme immunitaire
DE3145007A1 (de) Immobilisierte biologisch aktive substanzen und ihre verwendung
EP1003787B1 (fr) Agent pour le traitement et/ou la prophylaxie de troubles de la microcirculation
DE69836679T2 (de) Peptide zur behandlung des systemischen lupus erythematosus
DE102004042894A1 (de) Verwendung von Blockern der NKG2D-Rezeptor-/NKG2D-Liganden-Interaktion bei Autoimmunerkrankungen
US20100285146A1 (en) Peptides and methods for the treatment of systemic lupus erythematosus
WO2000039154A2 (fr) Peptides du recepteur at1 et son utilisation en cas de preeclampsie et d'hypertension maligne
EP0951481B1 (fr) Utilisation de substance a effet immunomodulateur pour le traitement de la sclerose lateral amyotrophique
Nishihara et al. Masugi nephritis produced by the antiserum to heterologous glomerular basement membrane: I. Results in mice
CH664496A5 (de) Material zur entfernung von immunkomplexen aus dem blut oder aus plasma.
US20120165781A1 (en) Targeted apheresis for the treatment of rheumatoid arthritis
EP1532272A2 (fr) Marqueur immunitaire de diagnostic et de traitement en liaison avec les reactions d'un greffon
DE68914513T2 (de) Gerät zur Modifikation einer Plasmazusammensetzung und Remodellierung.
DE19653669A1 (de) Adsorptionsmatrix, ihre Herstellung und ihre Verwendung zur Entfernung von Immunglobulinen aus biologischen Flüssigkeiten
WO2005025650A1 (fr) Dispositif de prelevement par apherese

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR

121 Ep: the epo has been informed by wipo that ep was designated in this application
AK Designated states

Kind code of ref document: C1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: C1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR

CFP Corrected version of a pamphlet front page
CR1 Correction of entry in section i
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP