Fatiha ELOUAAI

Laboratoire de Biologie Appliquée et Sciences de l’Environnement, Equipe de Recherche Santé et Environnement. Faculté des Sciences et Technique. BP: 416, 90001 Tanger. Email : elouaai@fstt.ac.ma

Abstract

Background: Nucleo-protein instead of DNA could be a major antigenic system at work in the pathogenesis of lupus disease with T cells sensitised against proteins associated to DNA in chromatin, playing a pivotal role.
Objective: To investigate in young lupus-prone mice that share a genetic background for lupus but do not develop early anti-chromatin autoimmunity and rapid glomerulonephritis, the effects of immunisations with DNA-free histones or nucleosomes on the development of autoimmunity to chromatin.
Methods: To address this question, Male and female NZB mice, female MRL-Mp+/+ mice, female BXSB mice and female Balb/c mice were immunised with histones or nucleosomes at 9, 11 and 13 weeks of age. Autoantibodies were investigated in plasma and the development of albuminuria was looked for from 14 to 21 weeks of age. Immunofluorescent studies were done on kidney at 21 weeks of age.
Results: We observed in the three lupus-prone strains of mice but not in control Balb/c mice: (1) an autoimmune responses against nucleosomes, histones and DNA after immunisation with nucleosomes; (2) an auto-immune response not only against histones, but also against DNA after immunisation with histones. The induction of anti-chromatin autoimmunity after immunisation with nucleosomes or histones was followed by the appearance of albuminuria, and by the deposition of immunoglobulins and complement in a granular pattern in glomeruli. Conclusion: Lupus-prone mice but not normal mice can develop autoimmunity against proteins associated to DNA in chromatin that triggers anti-DNA antibodies and subsequent development of immune complex nephritis.

Key words: Lupus mice, autoimmunity, autoantibodies, chromatin, glomerulonephritis, apoptosis