Antibody-mediated injury to proximal tubules in Heymann nephritis.

Antibody-mediated injury to proximal tubules in Heymann nephritis. To evaluate the hypothesis that antibody-mediated damage to proximal tubules (PT) could be a feature of Heymann nephritis (HN), we studied the kidneys of rats in different stages of the disease by light, immunofluorescence (IF), transmission, and scanning electron microscopy. The observations of morphology were correlated with titers of circulating antibodies directed against the brush border (BB) and with proteinuria. Antibody titers reached a maximum 5 to 7 weeks after immunization with Fx1A, coincident with the onset of proteinuria. IgG and C3 were deposited along the BB of PT in all animals within the first week of proteinuria. BB antibodies were present in the urine of those rats. As antibody titers declined, a decrease in the extent of in vivo IgG deposition along the BB was also noted. The results of indirect IF tests, by using BB antibodies on kidneys of rats with HN of 3 to 4 months' duration, suggested extensive loss of the BB antigen(s) from the PT. Numerous granular deposits of IgG were present along the basement membrane of PT at that time. Study of kidney histology revealed that deposition of IgG and C3 along the BB of PT was associated with extensive loss of microvilli, as well as degeneration and proliferation of PT cells. Subepithelial electron-dense deposits were present along the basement membrane of PT. In rats with HN of more than 4 months' duration, with little or no circulating BB antibodies and persistent proteinuria, IgG and C3 were found in minimal amounts along BB. Examination by light and electron microscopy provided evidence of partial recovery of PT lesions in those kidneys. Rats with similar proteinuria resulting from chronic serum sickness did not have similar abnormalities of PT. These observations are consistent with the interpretation that, in rats with HN, BB antibodies induce cytotoxic injury to PT. Lesions des tubules proximaux a mediation par anticorps dans la nephrite de Heymann. Pour evaluer l'hypothese selon laquelle des lesions des tubes proximaux (PT) ayant des anticorps comme mediateurs pourraient etre une caracteristique de la nephrite de Heymann (HN), des reins de rats a differentes etapes de la maladie ont ete etudies en microscopie photonique, d'immunofluorescence (IF), electronique a transmission, et a balayage. Les observations morphologiques ont ete correlees avec les titres d'anticorps circulants diriges contre la bordure en brosse (BB) et avec la proteinurie. Les titres d'anticorps ont atteint un maximum 5 a 7 semaines apres l'immunisation avec Fx1A, en coincidence avec l'installation de la proteinurie. IgG et C3 etaient deposes le long de BB du tube proximal chez tous les animaux dans la premiere semaine de la proteinurie. Des anticorps anti BB etaient presents dans l'urine de ces rats. Au fur et a mesure que les titres d'anticorps ont baisse, il a ete observe une diminution des depots d'IgG in vivo le long de BB. Les resultats des tests IF indirects, utilisant des anticorps anti BB sur les reins de rats atteints de HN depuis 3 a 4 mois, suggerent une perte importante des antigene(s) de BB du tube proximal. De nombreux depots granulaires d'IgG sont observes le long de la membrane basale du tube proximal a ce stade. L'etude de l'histologie renale revele que le depot d'IgG et de C3 le long de BB du tube proximal est associe a une perte importante de microvillosites et a la degenerescence et la proliferation des cellules du tube proximal. Des depots denses sous-epitheliaux ont ete observes le long de la membrane basale du tube proximal. Chez les rats atteints de HN depuis plus de 4 mois, avec peu ou pas d'anticorps anti BB circulants et une proteinurie persistante, de l'IgG et du C3 ont ete observes en quantites faibles le long de BB. L'examen en microscopie photonique et electronique a montre des signes de recuperation partielle des lesions du tube proximal. Les rats ayant une proteinurie semblable, consequence d'une maladie serique chronique, n'ont pas ces anomalies du tube proximal. Ces observations sont compatibles avec l'interpretation selon laquelle chez les rats atteints de HN les anticorps anti BB produisent des lesions cytotoxiques du tube proximal.