Antigen-antibody systems

A15. Alspaugh, M. A., and Maddison, P., Resolution of the identity of certain antigen-antibody systems in systemic lupus erythematosus and Sjogren s syndrome An interlaboratory collaboration. Arthritis Rheum. 22, 796-798 (1979). 

We selected various diseases for discussion. Rather than a litany, the list is somewhat eclectic. We summarize findings in those diseases in which considerable clinical experience with laboratory tests has accumulated and in which immune complex testing has been shown to bear some clinical relevance to the disease (as defined in the introduction). Our emphasis is on those diseases in which immune complexes appear to have a definite pathologic role, the antigen-antibody system has been well defined, or testing for immune complexes is of some value in clinical management. 

Although most of these immune complex materials appear to be combinations of IgG-IgG rheumatoid factor or IgG-IgM rheumatoid factor, other antigen-antibody systems may be important as well. The majority of patients with seropositive rheumatoid arthritis have antibodies to nuclear antigens present in Epstein-Barr virus-infected human cell lines (All, C6, N4, T4). Indeed, some rheumatoid factors appear to have dual specificity for both autologous IgG and these nuclear antigens (A13). Other, as yet unknown, types of complexes may be important as well (L3). 

In spite of the strong evidence for the role of DNA/anti-DNA complexes in causing the kidney lesions of systemic lupus (A6, K13, K15, W19), it is not certain that the material assayed in serum as immune complexes is actually composed of DNA linked to specific antibody. Several groups have demonstrated DNA (D2) or anti-DNA (H10) in immune complex material from sera, but careful studies by others have failed to repeat these findings (A7, H27, 18). DNA, by itself, does not persist in the circulation (G10, 17). Because of the multiplicity of autoantibodies found in lupus, any of a number of antigen-antibody systems may be involved (T4). Based on direct examination and the reactivity patterns with various immune complex assays, the immune complex material found in systemic lupus tends to be macromole-cular (>19 S) and complement fixing (A5, A7, C5, D2, El, F12, Gl, L2, M10, N6, T15). 

Rizzetto, M., Canese, M.G., Arico, S., Crivelli, O., Trepo, C., Bonino, F., Verme, G. Immunofluorescence detection of new antigen-antibody system (8/anti-8) associated to hepatitis B virus in liver and in serum of HBsAg carriers. Gut 1977 18 997-1003... 

Berg, P.A., Klein, R. Antimitochondrial antibodies in primary biliary cirrhosis and other disorders definition and clinical relevance. Dig. Dis. 1992 10 85-101 Mitochondrial antigen/antibody systems in primary biliary cirrhosis revisited. Liver 1995 15 281-292... 

Another example of new sorbents is the molecular imprinted polymers (MIP) from the work of Siemann and co-workers (1996). They synthesized a methacrylic acid-ethylene glycol dimethacrylate copolymer with atrazine as an imprint molecule. Imprint synthesis entails polymerization around an imprint species with monomers that are selected for their ability to form specific and definable interactions with the imprint molecule. The atrazine is chemically removed from the polymer leaving holes or cavities. The cavities are formed in the polymer matrix whose size and shape are complementary to that of the imprint molecule (Siemann et al., 1996). These recognition sites enable the polymer to rebind the imprint species selectively from a mixture of closely related compounds, in many instances with binding affinities approaching those demonstrated by antigen-antibody systems. 

For every particular antigen-antibody system the maximum binding of antibody per ml of gel and the optimum conditions (ionic strength, pH, temperature, solvent conditions) for the elution of the antibodies should be determined in a systematic way in pilot studies. 

Is potentially applicable to all microorganisms in which an antigen-antibody system can be demonstrated. Successful application has been reported with viruses (yellow fever, rabies), parasitic forms (amoebae, toxoplasma), and fungi. 

The detection of thyroid autoantibodies is important in the diagnosis of chronic lymphocytic thyroiditis (Hashimoto s disease) and the rarer forms of autoimmune thyroid disease, as the earlier reviews showed (D6, H2, 014). There are three antigen-antibody systems to be considered, namely, the two antibodies reacting with thyroid colloid [thyro-globulin and second colloid antigen (CA2), respectively], and in addition the antibody reacting with thyroid microsomes. 

Let us assume that our idealized antigen-antibody system consists of a solution containing antigen molecules A, antibody molecules B, soluble complex molecules A B, and molecules AB in equilibrium with a precipitate AB. We ignore other complexes A3B2, AaB, AB2, etc., and the known heterogeneity of antibody molecules in a serum. 

It is shown in the original paper how this equation (with K" = 0) accounts for many observed properties of antigen-antibody systems. 

Solubility of the precipitate in excess of antiserum has been reported for a few systems, such as diphtheria toxin and horse antitoxin, but not for antigen-antibody systems in general. Theoretical considerations indicate that solubility in antibody excess should occur for antigens wi small valence (such as the dihaptenic substances of Table IV) but not for antigens with large valence, which would only witii difificulty be saturated with antibody to form a soluble complex. 

The above treatment is in fact likely to be too crude as results from a more detailed study of electron transport in the absence of the enzyme in the antigen-antibody system depicted in Sch. 6. In fact, the average plane where the PEG chains are anchored is significantly different from... 

L. Wide, Solid-phase antigen-antibody systems, in K. E. Kirkham,... 

The complement system has the ability to combine irreversibly with antigen-antibody complexes. If the antigen is a protein component of the sheep erythrocyte cell surface, this combination induces lysis of the erythrocyte and thus offers an excellent quantitative indication of complement fixation. After incubation of the complement with the antigen-antibody complex under study, its fixation is studied by evaluating its residual haemolytic activity when the lytic antigen-antibody system is added. Since the concentrations of antibodies in the first system and of complement remain constant, haemolysis will be inversely proportional to the amoimt of antigen added to the incubation mixture (Table 1). 

Since the end of 1950s, the Ouchterlony method (Ouchterlony 1953) has been widely used with a large variety of antigen-antibody systems bacteria, moulds, yeasts and other organic material with antigenic properties. The fact that the Ouchterlony method is of low cost and is easy to use and to reproduce explains the long-term use of this technique. 

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