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.
Zhang
W
W
Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
Frank
M B
MB
Reichlin
M
M
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