Autoantibodies to DFS 70 kd/transcription coactivator p75 in atopic dermatitis and other conditions

Background: Sera of patients with atopic dermatitis (AD) were found to have autoantibodies that reacted with tissue culture cell substrates in immunohistochemistry to display a characteristic pattern of nuclear distribution of dense fine speckles. The sera also recognized a 70-kd protein on Western immunoblots, and the antigen was termed dense fine speckles 70 kd (DSF70). Objective: Because spontaneously occurring autoantibodies could be immune responses to proteins that might be participating in the disease process, it was of interest to identify the antigens driving the autoimmune antibody response. Methods: A serum containing high-titer antibodies to DFS70 was used to immunoscreen a complementary (c)DNA expression library to isolate cDNA encoding the antigen. After the cDNA was isolated, this was used to express recombinant protein to determine the prevalence of antibody in AD and other conditions. Results: Thirty percent of patients with AD were found to have antibody to recombinant DFS70 in Western immunoblots. Sixteen percent of patients with asthma and 9% of patients with interstitial cystitis had antibodies of the same specificities. The cDNA encoding DFS70 was identical to a transcription coactivator called p75, which had been shown to be required for RNA polymerase II–dependent transcription. Another important finding was that IgE antibodies to DFS70 were also present in AD sera. Conclusion: It is suggested that a common basis for the presence of autoantibodies to DFS70 might be related to AD in asthma, interstitial cystitis, and other conditions. A possible role of this antigen-antibody system in pathogenesis remains to be demonstrated, but it appears to be a marker for a subset of patients with AD. (J Allergy Clin Immunol 2000;105:1211-20.)