LUPUS AUTOANTIBODIES TO NATIVE DNA CROSS-REACT WITH THE A-SNRNP AND D-SNRNP POLYPEPTIDES

Antibodies to native DNA (nDNA) in sera from patients with systemic lu pus erythematosus have been found to frequently correlate with antibod ies to the A and D SnRNP proteins measured in Western blot assays. 40 of 54 SLE (74.1%) sera with anti-nDNA bound to A and D proteins, while 9 of 113 sera (8%) without anti-nDNA bound the A and D proteins, P < 10(-8) by Fisher's exact test. Antibodies to nDNA correlated closely w ith anti-a and anti-D in seven of eight patients followed sequentially , r = 0.7865. Nine human polyclonal anti-nDNA populations were isolate d from DNA cellulose columns. Seven reacted equally with A and D, and two reacted predominantly with D. Two of three murine monoclonal anti- DNA antibodies isolated from NZB/NZW F-1 hybrid mice bound A and D equ ally in Western blot with a titer > 1/40,000. These reactions were dir ected to the unfolded A and D proteins measurable in Western blot sinc e these monoclonals (and several of the human anti-nDNA populations) f ailed to react with native U-1 RNP in ELISA or in RNA immunoprecipitat ion experiments. These newly recognized cross reactions of anti-nDNA m ay amplify the immune response to DNA and be part of the original immu nogenic drive.