Advertisement

Research Article Free access | 10.1172/JCI111004

Neoantigen of the polymerized ninth component of complement. Characterization of a monoclonal antibody and immunohistochemical localization in renal disease.

R J Falk, A P Dalmasso, Y Kim, C H Tsai, J I Scheinman, H Gewurz, and A F Michael

Find articles by Falk, R. in: JCI | PubMed | Google Scholar

Find articles by Dalmasso, A. in: JCI | PubMed | Google Scholar

Find articles by Kim, Y. in: JCI | PubMed | Google Scholar

Find articles by Tsai, C. in: JCI | PubMed | Google Scholar

Find articles by Scheinman, J. in: JCI | PubMed | Google Scholar

Find articles by Gewurz, H. in: JCI | PubMed | Google Scholar

Find articles by Michael, A. in: JCI | PubMed | Google Scholar

Published August 1, 1983 - More info

Published in Volume 72, Issue 2 on August 1, 1983
J Clin Invest. 1983;72(2):560–573. https://doi.org/10.1172/JCI111004.
© 1983 The American Society for Clinical Investigation
Published August 1, 1983 - Version history
View PDF
Abstract

A monoclonal antibody to a neoantigen of the C9 portion of the membrane attack complex (MAC) of human complement has been developed and characterized. The distribution of this neoantigen was assessed by indirect immunofluorescence microscopy in nephritic and nonnephritic renal diseases. The antibody (Poly C9-MA) reacted on enzyme-linked immunosorbent assay (ELISA) with a determinant in complement-activated serum that was undetectable in normal human serum (NHS). Zymosan particles incubated in NHS had positive immunofluorescent staining with Poly C9-MA; however, binding of Poly C9-MA was not observed with zymosan particles incubated in sera deficient in individual complement components C3, C5, C6, C7, C8, or C9. Reconstitution of C9-deficient sera with purified C9 restored the fluorescence with Poly C9-MA. Poly C9-MA reacted positively by ELISA in a dose-dependent manner with purified MC5b-9 solubilized from membranes of antibody-coated sheep erythrocytes treated with NHS but not with intermediate complement complexes. Poly C9-MA also reacted in a dose-dependent manner on ELISA and in a radioimmunoassay with polymerized C9 (37 degrees C, 64 h) (poly C9) but not with monomeric C9. Increasing amounts of either unlabeled poly C9 or purified MC5b-9 inhibited the 125I-poly C9 RIA in an identical manner. These studies demonstrate that Poly C9-MA recognizes a neoantigen of C9 common to both the MAC and to poly C9. By immunofluorescence, Poly C9-MA reacted minimally with normal kidney tissue in juxtaglomerular loci, the mesangial stalk, and vessel walls. Poly C9-MA stained kidney tissue from patients with glomerulonephritis in a pattern similar to that seen with polyclonal anti-human C3. In tissue from patients with nonnephritic renal disease--diabetes, hypertension, and obstructive uropathy--Poly C9-MA was strongly reactive in the mesangial stalk and juxtaglomerular regions, tubular basement membranes, and vascular walls. Poly C9-MA binding was especially prominent in areas of advanced tissue injury. Poly C9-MA frequently stained loci where C3 was either minimally present or absent. These studies provide strong evidence for complement activation not only in nephritic but also in nonnephritic renal diseases.

Images.

Browse pages

Click on an image below to see the page. View PDF of the complete article

Version history
  • Version 1 (August 1, 1983): No description
Advertisement
Advertisement