SELECTION OF A GENE FOR APOLIPOPROTEIN A1 USING AUTOANTIBODIES FROM APATIENT WITH SYSTEMIC LUPUS-ERYTHEMATOSUS

Objective. To investigate immunoreactivity of systemic lupus erythemat osus (SLE) sera with apolipoprotein A1, (Apo A1), the major lipid-bind ing protein of high-density lipoprotein (HDL). Methods. Since early at tempts to identify Apo A1 autoantibodies using standard enzyme-linked immunosorbent assay (ELISA) and immunoblotting techniques had been uns uccessful, a mouse complementary DNA lambda phage expression library w as screened. Results. A selected clone (MA1) was found to have 82% DNA sequence homology to a segment of human Apo A1. Since there were nonc onservative substitutions in the MA1 protein and lack of a complete se quence, it was possible that the SLE patient's antibodies were binding MA1 epitopes that were shared by the complete human protein but had n ot been conformationally accessible using the earlier techniques. Thus , gamma-irradiated ELISA plates were used as an alternative antigen-bi nding surface for intact human Apo A1, and high-titer anti-human Apo A 1 autoantibodies were then identified in the sera of 5 more SLE patien ts. Conclusion. These findings show that Apo A1 is immunogenic. Apo A1 antibodies may play a role in the decreased HDL levels and Apo A1:Apo B ratios previously reported to occur in subgroups of SLE patients.