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Shared idiotypic determinant in mono- and polyclonal anti-phospholipid antibodies with lupus anticoagulant activity
F Wisløff1, K E Sletnes, T Michaelsen
1Haematological Research Laboratory, Ullevål Hospital, University of Oslo, Norway.
Of 42 purified human myeloma proteins tested, two (IgG3 Her and IgM Mag) were found to possess strong lupus anticoagulant (LA) and anti-cephalin activity, as assessed by a dilute activated partial thromboplastin time (dAPTT) and ELISA test, respectively. For these proteins, we confirmed the observation reported by others that LA activity is present in the antigen-binding (Fab) portion of the immunoglobulin molecule. Rabbit anti-idiotype antibodies against IgG3 Her inhibited the anti-cephalin activity of this protein, suggesting that the anti-cephalin activity of IgG3 Her depends on the hypervariable part of the immunoglobulin and thus most probably is a true antigen-antibody reaction. The anti-Her idiotype antibodies were also able to bind to and inhibit the anti-cephalin activity of IgM Mag. ELISA binding and inhibition experiments showed that the anti-idiotype antiserum contained at least two sets of anti-idiotypes; one set that recognizes a cross-reactive idiotype shared by IgG3 Her and IgM Mag, and another set that seems to be unique to the immunizing protein IgG3 Her. Both sets of anti-idiotype antibodies also bound weakly to polyclonal (patient) IgG, indicating an idiotypic cross reaction.
Of 42 purified human myeloma proteins tested, two (IgG3 Her and IgM Mag) were found to possess strong lupus anticoagulant (LA) and anti-cephalin activity, as assessed by a dilute activated partial thromboplastin time (dAPTT) and ELISA test, respectively. For these proteins, we confirmed the observation reported by others that LA activity is present in the antigen-binding (Fab) portion of the immunoglobulin molecule. Rabbit anti-idiotype antibodies against IgG3 Her inhibited the anti-cephalin activity of this protein, suggesting that the anti-cephalin activity of IgG3 Her depends on the hypervariable part of the immunoglobulin and thus most probably is a true antigen-antibody reaction. The anti-Her idiotype antibodies were also able to bind to and inhibit the anti-cephalin activity of IgM Mag. ELISA binding and inhibition experiments showed that the anti-idiotype antiserum contained at least two sets of anti-idiotypes; one set that recognizes a cross-reactive idiotype shared by IgG3 Her and IgM Mag, and another set that seems to be unique to the immunizing protein IgG3 Her. Both sets of anti-idiotype antibodies also bound weakly to polyclonal (patient) IgG, indicating an idiotypic cross reaction.