Immunization with a common epitope of nRNP a induces lupus autoimmunity
Systemic lupus erythematosus is an autoimmune disorder characterized by the production of large amounts of autoantibodies. Over 40% of lupus patient sera contain anti-RNP antibodies. Two binding patterns to nRNP in patients have been found, one complex with binding to many regions and one relatively simple with a substantial portion of the response being directed against two sequences. These sequences are termed (A3) LVSRSLKMRGQAF and (A6) ERDRKREKRKPKS. This limited autoimmune response is of interest because of its association with more severe clinical disease and nephritis. New Zealand White rabbits have been immunized with either the A3 or A6 peptides. The immunized rabbits first developed antibodies that bind with the peptide of immunization. With boosting, the immune response of rabbits immunized with the A3 peptide spread to other common antigenic regions of nRNP A. These regions of nRNP A bound by A3 immunized rabbits are very similar to common epitopes in human SLE. These A3 immunized rabbits also develop antibodies to common antigenic regions of nRNP 70k, nRNP C, Sm B/B', and Sm D. However, rabbits immunized with the A6 peptide have thus far developed antibodies only to the peptide of immunization. Immunization with the A3 peptide of nRNP A, but not the A6 peptide, appears to break tolerance to the rabbits' own spliceosomal complex. This disease model may help explain the pathogenesis and etiology of lupus in man and assist in the evaluation of the mechanism of breaking tolerance in SLE.
James, JA; Gross, TF; Davis, AL; McClain, MT; Harley, JB
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