title: Significance of anti-nuclear and anti-extracellular matrix autoantibodies for albuminuria in murine lupus nephritis; a longitudinal study on plasma and glomerular eluates in MRL/l mice.
abstract: The relationship between autoantibody reactivities and nephritis in systemic lupus erythematosus (SLE) is unclear. We studied MRL/l mice which developed a considerable albuminuria (either mice with short ( < 1 week) or heavy and prolonged (3 weeks) albuminuria) and compared them with non-albuminuric age-matched controls, with young (12 weeks old) non-albuminuric mice and with mice which were followed for 36 weeks and did not develop albuminuria. In a longitudinal prospective study on plasma samples we correlated a variety of anti-nuclear reactivities and reactivities against extracellular matrix (ECM) components, with the onset of albuminuria. We found that at the onset of albuminuria, anti-DNA was higher while anti-nucleosome and anti-H2A/H2B-DNA subnucleosome reactivities were lower compared with age-matched non-albuminuric mice. We also studied glomerular eluates of these mice in ELISA and in indirect immunofluorescence (IF). In the eluates we found with IF that anti-glomerular basement membrane (GBM)-tubular basement membrane (TBM) antibodies were already present in 12-week-old non-albuminuric mice. These eluates showed no anti-nuclear antibodies. In eluates of albuminuric mice more immunoglobulin was deposited, and anti-ECM, anti-DNA and anti-nucleosome reactivities were higher than in eluates of age-matched non-albuminuric mice. The deposition of anti-nucleosome antibodies preceded the deposition of anti-DNA antibodies since they were deposited to a greater extent in mice with a short albuminuria. We conclude that anti-GBM-TBM antibodies are the first autoantibodies that deposit in glomeruli of MRL/l mice at an early age. The onset of albuminuria is associated with additional deposition of both anti-ECM and anti-nuclear (anti-nucleosome and anti-DNA) antibodies, but the difference with non-albuminuric mice seems to be more quantitative than qualitative.
authors.affiliation: Division of Nephrology, University Hospital Nijmegen, The Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: van Bruggen
authors.forename: C
authors.initials: C
authors.lastname: Kramers
authors.forename: M N
authors.initials: MN
authors.lastname: Hylkema
authors.forename: R J
authors.initials: RJ
authors.lastname: Smeenk
authors.forename: J H
authors.initials: JH
authors.lastname: Berden
mesh_terms: D000419:Albuminuria / Q000276:immunology*; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood* / Q000737:chemistry; D001323:Autoantibodies / Q000097:blood* / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000276:immunology*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D007678:Kidney Glomerulus / Q000276:immunology*; D008137:Longitudinal Studies; D008181:Lupus Nephritis / Q000276:immunology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies