Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1997-04-11
1998-09-08
Saunders, David
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
435 75, 435 794, 435 795, 435962, 436509, 436512, 436513, 436518, 436536, 436825, G01N 33536, G01N 33543
Patent
active
058043918
DESCRIPTION:
BRIEF SUMMARY
DESCRIPTION
The invention concerns the use of a composition composed of several different antibodies or/and antibody fragments as a reagent to reduce interferences caused by rheumatoid factors in an immunochemical method.
The mammalian organism contains various classes of antibodies which are formed by the B cells of the immune system to defend against antigens. The antibody molecules are composed of one or several sets of four polypeptide chains, two heavy chains and two light chains which are linked together via disulfide bridges.
Antibodies are generally divided into the classes G, M, A, D and E. These five immunoglobulin classes differ in their heavy chain which is denoted .gamma., .mu., .alpha., .delta. and .epsilon. chain. In addition there are also immunoglobulin subclasses in the case of IgG, IgA and IgM.
Antibodies of the IgG class constitute 70 to 75% of the total immunoglobulin in normal human serum (corresponding to 8 to 16 mg/ml). They are mainly formed as the secondary immune response of the organism to an infection.
Antibodies of the IgM class make up ca. 10% of the immunoglobulin present in human serum and have a pentameric structure. These antibodies appear very early after an infection so that their determination is important for the early detection of diseases.
The immunoglobulins of the IgA class form about 15 to 20% of the immunoglobulin present in human serum and are the most important secretory immunoglobulin in saliva, milk and secretions of the urogenital region.
Antibodies of the IgD class are located on the membrane of circulating B cells and it is assumed that they play a role in autoimmune diseases.
Antibodies of the IgE class only occur in a very small amount in serum, but they play an important role in a number of allergic reactions such as asthma and hayfever.
The class-specific determination of immunoglobulins i.e. the selective determination of antibodies of one or several selected immunoglobulin classes or subclasses which are directed against a particular antigen in the presence of antibodies of other immunoglobulin classes or subclasses which are directed against the same antigen is of particular importance for the detection of particular diseases e.g. for the early diagnosis of infections, to differentiate between acute and healed infections and to make precise prognoses.
Methods for the class-specific determination of immunoglobulins are known. For this an immune component that is specific for a selected antibody class e.g. an antibody against the .mu. chain of human IgM can be coupled to a solid carrier and the antigen-specific immunoglobulin component can be detected by reaction with a directly or indirectly labelled antigen. In this type of method and also in other immunological test systems rheumatoid factors i.e. anti-IgG autoantibodies can interfere with the determination of the analyte. This can result in a falsification of the results and in particular false-positive reactions may occur.
EP-A-0 163 312 discloses an immunological test procedure in which particles which have an average size of .ltoreq.0.2 .mu.m and are coated with an interference-eliminating substance are used to inhibit an unspecific immune reaction. Immunoglobulins of human or animal origin are cited as interference-eliminating substances.
Henle et al. (Clin. Exp. Immunol. 36 (1979), 415-422) describe rheumatoid factors as the cause of false-positive reactions in tests for immunoglobulins that are specific for Epstein-Barr-Virus. It was possible to eliminate the interferences in some cases by using IgG-coated latex particles. Ho et al. (J. Clin. Microbiol. 27 (1989), 952-958) also describe the elimination of interference in an indirect ELISA for specific anti-Epstein-Barr-Virus antibodies by adding latex particles coated with human IgG.
Torfason and Diderholm (J. Med. Virol. 10 (1982), 157-170) disclose the fact that rheumatoid factors can lead to false results in the determination of IgM immunoglobulins against herpes simplex virus and cytomegalovirus. A mixture of protein A-Sepharose and pr
REFERENCES:
patent: 5466611 (1995-11-01), Toth
Patent Abstracts of Japan, vol. 006 No. 073, Aug. 5, 1982, JP,A,57 009723.
The Journal of Rhuematology, vol. 12, No. 3, Jun. 1985, pp. 427-431, Powell et al., An Improved assay for IGG Rhematoid Factor . . . .
Klemt Volker
Schlieper Dittmar
Schmitt Urban
Wiedmann Michael
Boehringer Mannheim GmbH
Saunders David
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