Concomitant early appearance of anti-ribonucleoprotein and anti-nucleosome antibodies in lupus prone mice.
OBJECTIVE
To gain insights on initial stages of the autoimmune response in lupus prone mice taking advantage of new sensitive and quantitative techniques for the detection of autoantibodies specific for RNA- (ribonucleoproteins) and DNA-protein (chromatin) complexes.


METHODS
DNA and nucleosome antibodies were detected by ELISA, antibodies to SmB, U1A-RNP, Ro52, Ro60 and La by a new radioligand assay, using de novo synthesized radio-labeled antigens.


RESULTS
Analysis of anti-chromatin (including anti-nucleosome, anti-dsDNA and anti-histone antibodies) and of anti-snRNP antibodies (including anti-U1A-RNP, anti-SmB, anti-Ro52, anti-Ro60, anti-La antibodies) was performed in sequential sera from B/W, MRL+/+, MRL Yaa and MRL lpr/lpr mice. In a cohort of 105 MRL+/+ mice of different ages, 59, 51, and 57 mice were positive for anti-nucleosome, anti-SmB and anti-U1A-RNP, respectively. None of them was positive for anti-dsDNA. Importantly, antibody positivities were not randomly distributed but were significantly clustered in individual mice. Appearance of DNA- and RNA-protein complex antibodies started at approximately 18-20 weeks of age, preceding that of the anti-dsDNA (or anti-histone) antibodies that only started at 30-32 weeks. Anti-nucleosome, anti-SmB and anti-U1A-RNP antibody responses did not display any cross-reactivity as demonstrated by inhibition and adsorption experiments.


CONCLUSIONS
These data indicate that anti-nucleosome and anti-snRNP antibodies appear early and concomitantly in lupus prone mice even though they do not share any cross-reactivity. These results fit with the assumption that their production is triggered by tightly physically associated nucleosomes and snRNP autoantigens contained in the same apoptotic bodies.
Laderach
Diego
D
INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Cedex 15, Paris, France.
Koutouzov
Sophie
S
Bach
Jean-François
JF
Yamamoto
Ana Maria
AM
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D002467:Cell Nucleus / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007700:Kinetics; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D051379:Mice; D009707:Nucleosomes / Q000276:immunology*; D012261:Ribonucleoproteins / Q000276:immunology*
D001323:Autoantibodies; D009707:Nucleosomes; D012261:Ribonucleoproteins