Abstract
In recent years defective function of the complement-mediated clearance of immune complexes (IC) has been reported in patients with immune complex disease. The defect has been found at different levels in the clearance system. An important event in this sequential system is the binding of C3-coated particles to C3 receptors on erythrocytes and phagocytes. This study focuses on immunochemical properties of IC-bound C3 that reflect the functional state of the molecule. Sera from patients with primary biliary cirrhosis (PBC), rhematoid arthritis (RA), and systemic lupus erythematosus (SLE) and from normal subjects were analyzed for their level of C3 precipitable in 2.7% (w/v) polyethylene glycol (PEG). The mean levels for the patient categories were significantly higher than that for the normal subjects. The immunochemical study revealed several differences among the different forms of PEG-precipitable C3. All forms expressed C3(D) antigens which are expressed by immune complex-associated and denatured forms but not by soluble physiological forms of C3. The expression of these antigens was proportionately lower for the complex-associated C3 of PBC compared to that of RA and SLE. Furthermore, employing monoclonal anti-C3(D) antibodies against the C3c and the C3d domain, distinct differences could be detected among all forms of PEG-precipitable C3. Sera from RA and SLE, in particular, contained PEG-precipitable C3 that exhibited distinctive immunochemical features with respect to these epitopes.
References
Kano K, Milgrom F: Immune complex diseases. Vox Sang 38:121, 1980
Ruddy S, Austen KF:In Complement and Its Components in Laboratory Diagnostic Procedures in Rheumatic Diseases, Ed 2, AS Cohen (ed). Boston, Little, Brown & Co., 1975
Schifferli JA, Yin C, Peters KD: The role of complement and its receptors in the elimination of immune complexes. N Engl J Med 315:486, 1985
Ross GD, Lambris JD, Cain JA, Newman SL: Generation of three different fragments of bound C3 with purified factor I and serum. J Immunol 129:2051, 1982
Nilsson UR, Beisswenger JG, Wyman-Caufman S: Altered antigenic expression of human C3 and C5, their subunits and fragments, following exposure to denaturing conditions. Mol Immunol 17:1319, 1980
Nilsson UR, Nilsson B: Analogous antigenic transition of C3 elicited by physiological binding and denaturation by detergent. J Immunol 129:2594, 1982
Nilsson B, Nilsson UR: SDS denaturation of complement factor C3 as a model for allosteric modifications occurring during C3b binding: Demonstration of a profound conformational change by means of circular dichroism and quantitative immunoprecipitation. Immunol Lett 13:11–14, 1986
Nilsson B, Nilsson UR: An assessment of the extent of antigenic analogy between physiologically bound C3 and C3 denatured by sodium dodecyl sulphate. Scand J Immunol 22:703, 1985
Ropes MW, Bennett GA, Cobb S, Jacox R, Jessar RA: 1958 revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis 9:175, 1958
Ran EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ: The 1982 revised criteria for the classification of systemic lupus erythematosus. Arth Rheum 25:1271, 1982
Scheuer PJ: Primary biliary cirrhosis. Proc R Soc Med 60:1257, 1967
Nilsson B, Svensson KE, Borwell P, Nilsson UR: Production of mouse monoclonal antibodies that detect distinct neoantigenic epitopes on bound C3b and iC3b but not on the corresponding soluble fragments. Mol Immunol 24:487, 1987
Mayer MM: Complement and complement fixation.In Experimental Immunochemistry, Kabat, Mayer (eds). Springfield, IL, Charles C Thomas, 1961, p 133
Laemmli UK, Favre MJ: Maturation of the head of the bacteriophage T4. J Mol Biol 80:575, 1972
Nilsson B, Lööf L, Nilsson UR: Identification of a non-proteolytically activated C3 with CR 1-binding properties in sera from subjects with primary biliary cirrhosis. Int Arch Allergy Appl Immunol 80:302, 1986
Lachmann PJ, Pangburn MK, Oldroyd RG: Breakdown of C3 after complement activation. J Exp Med 156:205, 1982
Aguado MT, Lambris JD, Tsokos GC, Burger R, Bitter-Suermann D, Tamerius JD, Dixon FJ, Theofilopoulus AN: Monoclonal antibodies against complement factor C3 neoantigens for detection of immune complexes and complement activation. J Clin Invest 76:1418, 1985
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nilsson, B., Bjelle, A., Lööf, L. et al. Quantitation and antigenic characterization of bound C3 of circulating immune complexes in systemic lupus erythematosus, rheumatoid arthritis, and primary biliary cirrhosis. J Clin Immunol 7, 420–426 (1987). https://doi.org/10.1007/BF00917020
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00917020