EP2293812A1 - Procédé d'isolement de cellules et d'agents pathogènes présents dans des liquides organiques - Google Patents
Procédé d'isolement de cellules et d'agents pathogènes présents dans des liquides organiquesInfo
- Publication number
- EP2293812A1 EP2293812A1 EP09753532A EP09753532A EP2293812A1 EP 2293812 A1 EP2293812 A1 EP 2293812A1 EP 09753532 A EP09753532 A EP 09753532A EP 09753532 A EP09753532 A EP 09753532A EP 2293812 A1 EP2293812 A1 EP 2293812A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- cells
- subunits
- immune complexes
- cic
- microorganisms
- 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.)
- Withdrawn
Links
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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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/564—Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
Definitions
- the invention relates to the production of separation systems for cells and / or pathogens based on subunits from circulating immune complexes (CIC).
- CIC circulating immune complexes
- CIC The functional basis for the immune response is based on the finely tuned interaction of local and systemically effective cellular and humoral components of innate and acquired immunity.
- CIC are the product of actions taken and reactions between these components, e.g. Antibodies and antigens, receptors and associated ligands, complement factors, albumin and other plasma constituents.
- Antibodies and antigens, receptors and associated ligands, complement factors, albumin and other plasma constituents e.g. Antibodies and antigens, receptors and associated ligands, complement factors, albumin and other plasma constituents.
- particulate agglomerates form, which are taken up and degraded by phagocytes.
- immunopathological events they are jointly responsible for the emergence and maintenance of a variety of acute and chronic inflammatory diseases.
- CICs are the final morphological product and thus a mirror image of ongoing or expired processes of immune regulation. This applies to the physiological, life-sustaining immune response as well as immunopathological processes that can lead to disease and death. In every individual, CICs can be detected in the blood. Excessive values are e.g. associated with rheumatoid arthritis.
- the subunits can be recovered gently. They retain their function of binding the respective reaction partner.
- the subunits can be up be coupled to a fixed matrix. This process is described in DE 19538641. It allows the removal of CIC and its subunits from the blood from the individuals from whom the CIC were obtained in the sense of affinity chromatography. In animal experiments with rats of the inbred strain BB / OK, an influence on immunoregulation by plasmapheresis could be demonstrated. BB / OK rats develop auto-aggressive ß-cell destruction similar to that of human juvenile diabetes (type 1 diabetes). CIC derived from plasmas were dissociated and covalently coupled to Sepharose.
- Antibodies Both the efficient defense of infectious agents and toxic substances and the homeostasis of healthy endogenous cells involve a number of immunocompetent cells and signaling systems. Antibodies, receptors and soluble mediators play an essential role in this complicated process. Antibodies are specifically directed against foreign and self-antigens and contribute to their elimination via various mechanisms (e.g., complement activation). The balance and proper function of the immune system depends on a number of factors.
- Autoimmunity is characterized by the loss of tolerance to the body's own tissue. Multiple endogenous and exogenous factors are involved in the dysregulation of the immune system. Many mechanisms involved in the pathogenesis of autoimmune diseases are discussed. Cross-reacting antibodies or an antigen-driven specific immune response are two of the many possibilities. The inadequate control of the potentially autoreactive cells and the presentation of autoantigens eventually lead to the formation of autoreactive cells and the production of pathogenic antibodies, resulting in considerable damage and often life-threatening consequences. Autoantibody-mediated disorders form a broad spectrum ranging from the functional impairment of a receptor to destructive systemic disease.
- the result of the dysregulation is also a significant increase in IgG anti-IgE autoantibodies correlated with the serum IgE level, which can be detected in circulating immune complexes (thus, up to 32% of total serum IgE in patients with atopic dermatitis in the form of IgG anti-IgE immune complexes).
- IgG anti-IgE immune complexes there is no correlation between the concentration of IgG anti-IgE immune complexes and the severity of the disease, due to the known heterogeneity of the autoantibodies in their ability to induce histamine release from basophils.
- IgG anti-IgE might be due to the high affinity of C1q IgGI and the Fc gamma receptor have an IgE-allergen complex eliminating function.
- the extracorporeal removal could be a further, at least in certain patients promising method of therapy.
- Specific antibodies are formed against the tumor proteins called neoantigens.
- neoantigens There are specific binding ligands.
- Antibodies such as ligands lead to the complexation of neoantigens.
- the immunological reaction is suppressed inter alia by the following mechanisms:
- immunosuppressive factors such as soluble tumor necrosis factor
- sTNFRs 5 receptor
- CEA neoantigens
- Neoplasms the blood concentration of neoantigen immunocomplex has prognostic significance.
- the condensation products of tumor action and body counteraction circulate as CIC's in the blood.
- virus immune complexes are taken up by phagocytes and reduced.
- viruses such as Dengue virus
- Neutralized herpesvirus IgG immune complexes induce the same IL6 release in macrophages as free viral DNA.
- a correlation was detected between the cerebellar immune complexes and the rheumatoid Artrithis (MAY et al., Rheumatology. 1994; 33: 27-31).
- Virus immune complexes play a pathogenic role in virus-induced immune complex diseases (eg, glomerulonephritis, Appel, GB, et al., NEJM, Feb. 18, 1993). Almost all patients suffering from chronic hepatitis C infection carry immune complex-bound HCV (MORITA T. et al., Hepato-gastroenterology, 1996, 43, 582-585), which can lead to permanent reinfection. A therapeutic influence of, usually chronic, viral infections with extracorporeal blood treatment procedures must therefore always remove the virus bound in the immune complex.
- the object of the invention is to provide a method, an arrangement and its use, on the basis of which, with different separation methods, cells, including pathogens, can be isolated or examined from body fluids. It is necessary in the first step to recognize the target cells.
- CIC CIC
- They are not just the final product intended for degradation in the biological reaction chain.
- CICs are also key to isolating cells from the blood of individuals related to the current status of cellular immune regulation.
- CIC subunits have been shown to bind to the surface of cells.
- the CIC are prepared by known methods, e.g. Precipitation method or obtained by means of protein A - Adsorbem from the plasma of individuals. After such isolation, the CICs are broken down into their biologically active constituents. This is preferably done by lowering the pH to ⁇ 3.0.
- the subunits can be prepared by known methods, e.g. Gel chromatography, separately and individually and mixed as a mixture of corresponding support materials, preferably microparticles, are suitable as solid support all available solid materials, in particular polystyrene or more preferably sepharose. With the aid of these "scavenger particles", cells can be separated from blood and other body fluids using different separation techniques In a second step, the cells can be characterized, cultured in vitro, subpopulated, manipulated, and used for further diagnostic or therapeutic purposes.
- Cell depletion by means of a continuous or discontinuous extracorporeal method for therapeutic use can also be carried out using the method according to the invention.
- Such systems are also reactivated by known methods and possible for multiple use.
- Figure 1 Total fraction of dissociated CIC coupled to particles and incubated with Mono Nuclear Cells (MNC) from donor JM to Ficoll gradient.
- MNC Mono Nuclear Cells
- Figure 2 Total fraction of dissociated CIC coupled to particles and incubated with whole blood from donor JM.
- FIG. 3 30-100kDa fraction of dissociated CIC coupled to particles and incubated with Mono Nuclear CeIIs (MNC) from donor JM to Ficoll gradient
- Figure 4 30-100kDa fraction of dissociated CIC coupled to particles and incubated with whole blood from donor JM.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Urology & Nephrology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Medicinal Chemistry (AREA)
- Rheumatology (AREA)
- General Physics & Mathematics (AREA)
- General Engineering & Computer Science (AREA)
- Pathology (AREA)
- Rehabilitation Therapy (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- External Artificial Organs (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
L'invention concerne un procédé, un ensemble et leur utilisation, visant à isoler ou à analyser, à l'aide de différents procédés de séparation, des cellules, y compris des agents pathogènes, présents dans des liquides organiques. A cet effet, un procédé destiné à isoler des virus, des micro-organismes et/ou des cellules somatiques présents dans des liquides organiques d'individus, comprend les étapes consistant à: (f) isoler des complexes immuns à partir du liquide organique d'un individu; (g) dissocier les complexes immuns isolés en sous-unités; (h) lier les sous-unités dissociées à un support solide, (i) incuber le support modifié (c) avec des cellules ou le liquide organique dudit individu (a), (j) isoler le support incubé (d) avec les cellules, les micro-organismes et/ou les virus liés auxdites sous-unités; et un ensemble selon l'invention destiné en particulier à un diagnostic ou à une thérapie spécifique à un patient comprend: un support, de préférence des microparticules; des sous-ensembles constitués de complexes immuns, de préférence des CIC (complexes immuns circulants) d'un individu, liés au support; des cellules, des micro-organismes et/ou des virus provenant du même individu, de préférence des MNC (cellules mononucléaires), liés auxdites sous-unités. L'invention concerne également l'utilisation d'un tel procédé et d'un tel ensemble.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102008025965A DE102008025965A1 (de) | 2008-05-30 | 2008-05-30 | Verfahren zur Isolierung von Zellen und Krankheitserregern aus Körperflüssigkeiten |
| PCT/DE2009/000719 WO2009143816A1 (fr) | 2008-05-30 | 2009-05-26 | Procédé d'isolement de cellules et d'agents pathogènes présents dans des liquides organiques |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP2293812A1 true EP2293812A1 (fr) | 2011-03-16 |
Family
ID=41198566
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP09753532A Withdrawn EP2293812A1 (fr) | 2008-05-30 | 2009-05-26 | Procédé d'isolement de cellules et d'agents pathogènes présents dans des liquides organiques |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US20110306034A1 (fr) |
| EP (1) | EP2293812A1 (fr) |
| DE (2) | DE102008025965A1 (fr) |
| WO (1) | WO2009143816A1 (fr) |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4551435A (en) * | 1983-08-24 | 1985-11-05 | Immunicon, Inc. | Selective removal of immunospecifically recognizable substances from solution |
| US5122112A (en) * | 1986-11-21 | 1992-06-16 | Imre Corporation | Antigen-specific removal of circulating immune complexes |
| DE19538641C2 (de) * | 1995-10-05 | 2000-09-21 | Privates Inst Bioserv Gmbh | Patientenspezifische Immunadsorber für die extrakorporale Apherese und Verfahren für deren Herstellung |
-
2008
- 2008-05-30 DE DE102008025965A patent/DE102008025965A1/de not_active Withdrawn
-
2009
- 2009-05-26 DE DE112009001907T patent/DE112009001907A5/de not_active Withdrawn
- 2009-05-26 WO PCT/DE2009/000719 patent/WO2009143816A1/fr active Application Filing
- 2009-05-26 US US12/995,256 patent/US20110306034A1/en not_active Abandoned
- 2009-05-26 EP EP09753532A patent/EP2293812A1/fr not_active Withdrawn
Non-Patent Citations (1)
| Title |
|---|
| See references of WO2009143816A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| DE112009001907A5 (de) | 2011-04-28 |
| DE102008025965A1 (de) | 2009-12-03 |
| WO2009143816A4 (fr) | 2010-02-25 |
| US20110306034A1 (en) | 2011-12-15 |
| WO2009143816A1 (fr) | 2009-12-03 |
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