Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 60, Issue 2, Pages 309-320Publisher
SPRINGER BASEL AG
DOI: 10.1007/s000180300026
Keywords
antibodies; autoantibodies; lupus; SLE; immunoglobulin genes; pathogenicity; autoimmunity; crystallography; computer models
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Funding
- NIA NIH HHS [AG13541] Funding Source: Medline
- NIGMS NIH HHS [GM32375] Funding Source: Medline
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Anti-DNA antibodies contribute to the pathology of systemic lupus erythematosus. Their depositon in tissue lesions could result from localization of preformed immune complexes of antibodies with DNA or nucleosomes, or from cross-reaction of anti-DNA antibodies directly with tissue proteins. Structural analyses contribute to understanding their pathogenic potential. Primary structures of lupus immunoglobulin G double-stranded DNA-binding autoantibodies are determined by immunoglobulin genes with mutated variable region segments, indicative of selection by immunizing antigen. Arginine, lysine and asparagine residues in complementarity-determining region favor DNA binding. Heavy-chain variable regions make major contributions to DNA binding; affinity and specificity of binding are modulated or can be abrogated by the light-chain variable domain. Crytallographic structure is known for a few antibody-DNA complexes and several ligand-free Fab fragments. Computer modeling supplements this limited information. Structural information of lupus antibody interactions with both DNA and cross-reacting molecules will support use of ligands to inhibit tissue deposition of the antibodies and prevent lesion formation in lupus.
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