Laboratory Investigation

Kidney International (1985) 27, 388–393; doi:10.1038/ki.1985.21

Possible involvement of terminal complement complex in active Heymann nephritis

Emile de Heer, Mohamed R Daha, Sucharit Bhakdi, Hervé Bazin and Leendert A van Es

Department of Nephrology, University Hospital Leiden, Leiden, The Netherlands; Institute of Medical Microbiology, University of Giessen, Giessen, West Germany; Experimental Immunology Unit, University of Louvain, Brussels, Belgium

Correspondence: Dr E de Heer, Department of Nephrology, University Hospital Leiden, 2333 AA Leiden, The Netherlands

Received 2 April 1984; Revised 25 July 1984.

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Abstract

Possible involvement of terminal complement complex in active Heymann nephritis. We investigated whether the appearance of various complement components in renal deposits of immune complexes correlated with the development of proteinuria in rats with active Heymann nephritis. Sequential kidney biopsy specimens and serum samples were obtained from Lewis rats immunized with Fx1A in complete Freund's adjuvant. Circulating antibodies against purified auto-antigen renal tubular epithelial glycoprotein, as measured by ELISA, were found in the circulation together with a diffuse granular deposition of IgG1, IgG2a, and IgG2b in the glomeruli within 2 weeks after immunization. Biopsy specimens taken 4 weeks after immunization showed diffuse deposition of C4 and C3, which indicated that activation of complement by the classical pathway had occurred. The detection of the C5b-9 complex of complement in glomerular deposits coincided with the development of abnormal proteinuria indicating that the glomerular damage in this autoimmune disease may be caused by complement-mediated lesions in the glomerular capillary walls.

Mise en jeux possible du complexe terminal du complément dans la néphrite active de Heymann. Nous avons cherché si l'apparition de diverses fractions du complément dans les dépôts rénaux d'immunscomplexes était corrélée au développement d'une protéinurie chez des rats atteints de la néphrite de Heymann. Des spécimens biopsiques rénales et des échantillons plasmatiques séquentiels ont été obtenus chez des rats Lewis immunisés avec Fx1A dans l'adjuvant complété de Freund. Des anticorps circulants contre G auto-antigène glycoprotéine de épithélium rénal tubulaire purifié, mesurés par ELISA, ont été trouvés dans la circulation en association à des dépôts granulaires diffus d'IgG1, IgG2a, et d'IgG2b dans les glomérules, 2 semaines après l'immunisation. Des spécimens biopsiques obtenues 4 semaines après l'immunisation ont montré des dépôts diffus de C4 et de C3, ce qui indiquait qu'une activation du complément par la voie classique s'était produite. La détection du complexe C5b-9 du complément dans les dépôts glomérulaires coïncidait avec le développement d'une protéinurie anormale ce qui indique que la lésion glomérulaire dans cette maladie auto-immune peut être due à des altérations à médiation complémentaire des parois capillaires glomérulaires.

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