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Production and characterization of human monoclonal anti-idiotype antibodies to anti-dsDNA antibodies

M B Frank

Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA

M Reichlin

Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA: Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA;Morris-Reichlin{at}omrf.ouhsc.edu

Anti-dsDNA autoantibodiesare 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-puri"ed 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.

Key Words: monoclonal antiidiotype to anti-dsDNA

Lupus, Vol. 11, No. 6, 362-369 (2002)
DOI: 10.1191/0961203302lu207oa


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