Production and characterization of human monoclonal anti-idiotype antibodies to anti-dsDNA antibodies.
Anti-dsDNA autoantibodies are the hallmark of systemic lupus erythematosus (SLE) and frequently correlate with disease activity. In this study we report the isolation and characterization of human anti-Id monoclonal antibody fragments as single-chain Fv fragments (scFv) against anti-dsDNA antibody. The anti-Id monoclonal antibodies, specific for anti-dsDNA antibodies, have been cloned from phage display antibody scFv libraries derived from a patient with SLE. The V gene repertoires were derived from the RNA obtained from the B cells of an SLE patient with anti-Ro/SSA and anti-La/SSB antibodies. Affinity-purified anti-dsDNA antibodies were used for selection of bacterial clones producing specific scFv antibody fragments against anti-dsDNA antibodies and little reactivity with normal IgG and other IgG antibodies by ELISA. The anti-Id antibody recognizes a public idiotope that is broadly cross-reactive with polyclonal and monoclonal anti-dsDNA antibodies. This binding was largely inhibited by dsDNA antigen. The anti-Id antibody inhibited anti-dsDNA binding to dsDNA antigen in immunoassays and in the Crithidia luciliae assay. The anti-Id scFv antibody fragments derived from human genes could modulate the pathogenicity of anti-dsDNA autoantibodies and may have therapeutic implications in SLE. They may also be used as probes in studies of the structure of the idiotype.
Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
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Zhang
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Frank
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Reichlin
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D000974:Antibodies, Antinuclear / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D003421:Crithidia; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007128:Immunoglobulin Fragments / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D007167:Immunotherapy; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000628:therapy; D019151:Peptide Library
D000888:Antibodies, Anti-Idiotypic; D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D007128:Immunoglobulin Fragments; D019151:Peptide Library; C055966:immunoglobulin Fv