A human cDNA expression library that was used to investigate the nature of autoantigens recognized by the serum from a patient with systemic lupus erythematosus revealed the presence of antibodies directed against two transcriptional regulation protein: DEK, a site-specific 45 kD DNA binding protein, likely involved in signal transduction and transcriptional regulation, and a novel 28 kD protein that showed a 94% homology with murine ALY, a nuclear protein that plays a role in regulating the activity of TCRalpha enhancer complex. Whereas autoantibodies directed to epitopes on DEK are commonly found in patients with pauciarticular onset juvenile rheumatoid arthritis, autoantibodies against ALY have not been described and their occurrence has led to the cloning of the cDNA sequence of the first member of the human ALY family.