TY - JOUR
T1 - Autoantibodies that bind glomeruli
T2 - Cross-reactivity with bacterial antigen
AU - Chowdhry, Iftikhar A.
AU - Kowal, Czeslawa
AU - Hardin, John
AU - Zhou, Zhijie
AU - Diamond, Betty
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/8
Y1 - 2005/8
N2 - 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. Conclusion. This study suggests that both DNA-binding and non-DNA-binding antibodies in SLE may be elicited by the same bacterial antigens.
AB - 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. Conclusion. This study suggests that both DNA-binding and non-DNA-binding antibodies in SLE may be elicited by the same bacterial antigens.
UR - http://www.scopus.com/inward/record.url?scp=23644459676&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=23644459676&partnerID=8YFLogxK
U2 - 10.1002/art.21143
DO - 10.1002/art.21143
M3 - Article
C2 - 16052539
AN - SCOPUS:23644459676
VL - 52
SP - 2403
EP - 2410
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
SN - 2326-5191
IS - 8
ER -