fr
Article scientifique
Anglais

Glomerulopathy induced by IgG3 anti-trinitrophenyl monoclonal cryoglobulins derived from non-autoimmune mice

Publié dansKidney international, vol. 45, no. 4, p. 962-971
Date de publication1994
Résumé

We have previously shown that murine IgG3 monoclonal autoantibodies with cryoglobulin activity, derived from lupus-prone mice, are able to induce glomerular lesions resembling the "wire-loop" lesion typically described for human lupus nephritis. In the present study, we have further assessed the nephritogenic potential of four IgG3 anti-hapten, trinitrophenyl (TNP), monoclonal antibodies (mAb) obtained from non-autoimmune mice immunized with TNP-conjugated foreign antigens. Our results showed that two of four IgG3 anti-TNP monoclonal cryoglobulins were capable of inducing glomerular lesions, characterized by voluminous intracapillary thrombi and mesangial deposition of PAS-positive materials, which differed from "wire-loop" lesions generated by IgG3 monoclonal cryoglobulins with autoantibody activities. These anti-TNP monoclonal cryoglobulins, however, failed to induce glomerular lesions when mice were kept at 37 degrees C after the mAb administration. This finding formally proves that the cryoglobulin activity is critically involved in the development of glomerular lesions induced by IgG3 anti-TNP mAb. In addition, we have demonstrated a remarkable difference in the nephritogenic activities of two IgG3 anti-TNP mAb, which exhibit a marked sequence homology in the variable regions of their heavy and light chains (91.5% and 99.1% at the amino acid level, respectively) and an identical isoelectric point. Our results indicate first, that IgG3 monoclonal cryoglobulins are able to generate two different kinds of glomerular lesions, and second, that a subtle difference in variable region sequences may determine not only the nephritogenic activities, but also the type of glomerular lesions mediated by IgG3 cryoglobulins.

Mots-clés
  • Animals
  • Antibodies, Monoclonal/genetics/immunology
  • Autoimmunity
  • Base Sequence
  • Cryoglobulins/ immunology
  • Glomerulonephritis/ immunology/pathology
  • Haptens/immunology
  • Immunoglobulin G/genetics/ immunology
  • Immunoglobulin Isotypes/genetics/immunology
  • Kidney Glomerulus/ultrastructure
  • Lupus Nephritis/etiology/immunology/pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Trinitrobenzenes/ immunology
Citation (format ISO)
FULPIUS, Thierry et al. Glomerulopathy induced by IgG3 anti-trinitrophenyl monoclonal cryoglobulins derived from non-autoimmune mice. In: Kidney international, 1994, vol. 45, n° 4, p. 962–971. doi: 10.1038/ki.1994.130
Fichiers principaux (1)
Article
accessLevelRestricted
Identifiants
ISSN du journal0085-2538
526vues
0téléchargements

Informations techniques

Création27/08/2010 13:34:32
Première validation27/08/2010 13:34:32
Heure de mise à jour14/03/2023 16:03:20
Changement de statut14/03/2023 16:03:19
Dernière indexation12/02/2024 19:17:06
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack