Immunization with 60kD Ro leads to a diversified immune response to several lupus autoantigens
Systemic lupus erythematosus is an autoimmune disorder characterized by the production of antibodies to ribonucleoproteins, including 60kD Ro (SS-A), La (SS-B), and 52kD Ro. Spliceosomal proteins, such as Sm and nRNP are also common targets of lupus autoimmune responses. We have immunized New Zealand White rabbits with purified bovine 60kD Ro in order to study the mechanism by which these antibodies arise. Rabbits so immunized not only developed antibodies to the immunogen, but also to other self proteins commonly recognized by lupus patients. Antibodies to nRNP are detected by ELISA and confirmed by Western Blot analysis. Antibodies to Sm are also present in these 60kD Ro immunized rabbits as detected by ELISA. These findings have also been confirmed by solid-phase peptide synthesis immunoassay. Rabbits immunized with 60kD Ro mount a diversified immune response to the overlapping octapeptides of the spliceosomal proteins. Antibodies like these are not found in sham immunized animals. Anti-nuclear antibodies and anti-native DNA are also present as measured by immunofluorescense. These results provide an interesting model of epitope spreading by immunizing with a single ribonucleoprotein which then induces production of antibodies to other important self proteins. This model may assist in the evaluation of the mechanism of epitope spreading in SLE.
Davis, AL; McClain, MT; Gross, TF; Harley, JB; James, JA
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