Widespread susceptibility among inbred mouse strains to the induction of lupus autoantibodies by pristane.
Unlike other agents associated with drug-induced lupus, the isoprenoid alkane pristane induces autoantibodies pathognomonic of lupus, including anti-Sm, anti-dsDNA, and anti-ribosomal P in BALB/c and SJL/J mice. The susceptibility of other strains of mice to pristane-induced lupus is unknown and is the focus of the present study. Anti-nRNP/Sm, anti-Su, and anti-ribosomal P autoantibodies were produced by most strains of mice surveyed within several months of pristane treatment, although there was marked interstrain variability in their frequencies, levels, and times of onset. In sharp contrast, the production of autoantibodies against the double-stranded RNA binding proteins NF45/NF90/p110 was restricted to B6 and B10.S mice. We conclude that pristane selectively induces lupus-specific autoantibodies in virtually any strain of mouse regardless of its genetic background. However, H-2-linked as well as non-H2 genes influenced the expression of individual autoantibody markers. The widespread susceptibility of pristane-treated mice to lupus autoantibody production and the relatively small effect of MHC are unique features of this chemically induced lupus syndrome, with potential implications for understanding the pathogenesis of autoantibodies in idiopathic human systemic lupus erythematosus.
Division of Rheumatology and Clinical Immunology, University of Florida, Gainesville, FL, USA.
M
M
Satoh
H B
HB
Richards
V M
VM
Shaheen
H
H
Yoshida
M
M
Shaw
J O
JO
Naim
P H
PH
Wooley
W H
WH
Reeves
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006183:H-2 Antigens / Q000235:genetics; D006239:Haplotypes; D006799:Housing, Animal; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D020014:K562 Cells; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains / Q000235:genetics* / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D010750:Phosphoproteins / Q000276:immunology; D012269:Ribosomal Proteins / Q000276:immunology; D013045:Species Specificity; D013729:Terpenes / Q000633:toxicity*
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001324:Autoantigens; D006183:H-2 Antigens; D007074:Immunoglobulin G; D010446:Peptide Fragments; D010750:Phosphoproteins; D012269:Ribosomal Proteins; D013729:Terpenes; C031937:phosphoprotein P2, ribosomal; C035690:ribosomal phosphoprotein P1; C054675:ribosomal protein P0; C009042:pristane