59 Insoluble DNA-like phosphorylated polyst~ene: specific anti-DNA antibodies ~teractions with from systemic patients lupus erythematosus D. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Letourneur and zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA M. Jozefowicz Laboratoire de Recherches sur les Macromol&ules, CSP Universit6 Paris-Nor& Avenue JB CMment, 93430 Villetaneuse. France Systemic lupus erythematosus (SLE) is an autoimmune disease. Antibodies directed mainly against DNA and/or phospholipids are present in the serum of SLE patients. Therefore phosphorylated polystyrene derivatives acting as DNA-like polymers should be able to interact with the SLE anti-DNA antibodies. Such functional polymers were synthesized and subsequently their interactions with the anti-DNA antibodies studied. Adsorption experiments performed with both anti-DNA antibodies and normal immunoglobulins showed high affinity constants of the phosphorylated polymer for anti-DNA antibodies (4 X 10’ M-‘) whereas for normal IgG the affinity was low (2 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA X IO5 M-l). Moreover, the interaction was specific involving the idiotypic moiety of the anti-DNA antibodies and an array of phosphoester groups at the surface of this biomaterial. Keywords: Phosphorylated polystyrene& antibodies, DNA Received 18 July 1990; revised 18 October 1990; accepted 20 November 1990 Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown origin, characterized by the plurality of its clinical manifestations’-3. Serologically, the presence of a wide variety of autoantibodies is commonly described4. Antibodies, belonging mainly to the IgG clas$, directed against double-stranded deoxyribonucleic acid (dsDNA) have been particularly associated with SLE, and are assumed to be involved in the pathogenesis of the disease3b6’7. However, several studies performed during the last decade have reported that monoclonal and polyclonal anti-DNA antibodies cross-reacted*-” with various nucleic acids, polynucleotides, phospholipids, bacteria” and cell-surface proteins13’ 14, These cross- reactions were due to a similarity in the antigen-binding sequence sites’j. On the other hand, functional synthetic polymers have been shown to develop specific interactions with various plasma proteins’“. These synthetic polymers substituted with specific chemical groups are able to interact with serine proteases involved in the coagulation cascade16B 17. Some insoluble derivatized polystyrenes present a high affinity for anti-factor VIII antibodies17. This work examined whether DNA antigen-like functional poiymers could be synthesized to interact specifically with the Fab fragment of SLE anti-DNA antibodies. We postulated that the interactions between the epitope of DNA molecule and the SLE antibodies Correspondence to Dr D. Letourneur 0 1992 Butterworth-Heinemann i_td 92/010059/05 involve the phosphodiester groups of the DNA molecules. This assumption is based on the fact that SLE anti-DNA antibodies are able to interact with dsDNA where the deoxyribosephosphate backbone is accessible to an antibody combining site but the purine and p~midine bases are not’. Moreover, the anti-DNA antibodies cross- reacted with biological molecules containing phosphate esters’* 15, Based on this assumption, we developed phosphorylated polystyrene derivatives where phospho- ester groups were linked to the styrene monomer via different spacers. We expected that these functional polymers were similar to the DNA-binding sites with regard to their antigen property. In the present study, we report some typical syntheses of the functional polymers which will be extensively described elsewhere. We have explored with these phos- phorylated resins, the systemic interactions developed with anti-DNA antibodies from the sera of SLE patients. We also compared the affinities of the anti-DNA antibodies to those of normal IgG on these functional polystyrene resins. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSR MATERIALS AND METHODS Materials Polystyrene. Polystyrene (PS) resins, cross-linked with 2% of divinyl- benzene, were commercially available from Fluka Inc. Biomaterials 1992, Vol. 13 No. 1