Autoantibodies that bind glomeruli: cross-reactivity with bacterial antigen.
OBJECTIVE
Systemic lupus erythematosus (SLE) is characterized by the production of multiple autoantibodies. Anti-DNA antibodies are associated with glomerulonephritis in SLE. It has been shown that anti-DNA antibodies cross-react with bacterial polysaccharide and, thus, might be elicited by microbial exposure. Non-DNA-binding antibodies also contribute significantly to the pathogenesis of lupus nephritis. The goal of this study was to characterize non-DNA-binding, kidney-binding antibodies.


METHODS
We generated a combinatorial library derived from spleen cells of a patient with SLE who had just previously received pneumococcal vaccine. The phage library was used in an in vivo biopanning technique to identify non-DNA-binding, kidney-binding antibodies. Antibodies were then analyzed for binding to bacterial polysaccharide and to renal antigens.


RESULTS
Eight antibodies were characterized that bound glomeruli, but not DNA. All antibodies isolated by this protocol were IgG class, suggesting that there is affinity maturation for glomerular binding. Four of the antibodies cross-reacted with pneumococcal polysaccharide. Six of the antibodies bound to renal antigens that have previously been reported to be cross-reactive with DNA; the other 2 bound to histone.


CONCLUSIONS
This study suggests that both DNA-binding and non-DNA-binding antibodies in SLE may be elicited by the same bacterial antigens.
Chowdhry
Iftikhar A
IA
Albert Einstein College of Medicine, Bronx, NY 10032, USA.
Kowal
Czeslawa
C
Hardin
John
J
Zhou
Zhijie
Z
Diamond
Betty
B
D000974:Antibodies, Antinuclear / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D003429:Cross Reactions; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007678:Kidney Glomerulus / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology
D000974:Antibodies, Antinuclear; D000942:Antigens, Bacterial; D001323:Autoantibodies; D007074:Immunoglobulin G; D011135:Polysaccharides, Bacterial