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Monoclonal antibodies against complement 3 neoantigens for detection of immune complexes and complement activation. Relationship between immune complex levels, state of C3 and numbers of receptor for C3b

Journal of Clinical Investigation (Impact Factor: 13.77). 11/1985; 76(4):1418-26. DOI: 10.1172/JCI112119
Source: PubMed

ABSTRACT C3-bearing immune complexes and C3 activation products were detected by using two monoclonal antibodies, one specific for a neoantigenic determinant on C3c and the other for C3d. To quantitate immune complexes, the anti-C3c or anti-C3d antibodies were fixed to microtiter plates and reacted with test plasma. The binding of C3-bearing immune complexes in this plasma was then measured with radioisotope- or enzyme-labeled anti-human IgG. To test for C3 breakdown products, solid-phase monoclonal antibody to the C3d neoantigen was reacted with EDTA-plasma samples, and fixed iC3b or C3d was measured with a polyclonal anti-C3 antibody. Patients with autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and Sjogren's syndrome, and paracoccidioidomycosis were found to contain immune complexes bearing C3b/iC3b or C3d. In most conditions, there were more C3d-containing immune complexes than C3b/iC3b. Although CR1 (C3b receptors) rapidly converted immune complex-bound iC3b to C3dg/C3d and lupus patients had reduced CR1, no correlation between the state of C3 on circulating immune complexes or levels of immune complexes and CR1 numbers was seen. However, levels of C3-fixing ICs correlated with levels of C3 activation products. This assay system with monoclonal antibodies to neoantigens expressed on activated, but not native, C3 provides sensitive and specific means for detecting and classifying C3-fixing immune complexes and for assessing C3 activation.

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Available from: John D Lambris, Aug 25, 2015
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    • "At present ANTI-C3 ELISA and the conglutinin test are the most used antigen-nonspecific assays able to detect CIC according to the immunoglobulin isotypes contained (IgG- CIC, IgM-CIC and IgA-CIC) (Iida et al., 1987; Ruddy and Moxley, 1994; Lock and Unsworth, 2000). Unfortunately, both tests can detect false positive results (Aguado et al., 1985; Holmskov et al., 1992). It is obvious that a new sensitive and easy performing test for quantitative assessment of IgM-CIC and IgA-CIC would be actual. "
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