Discovery of biomarkers for systemic lupus erythematosus using a library of synthetic autoantigen surrogates

•Peptoid libraries yield compounds that react with disease-specific IgG.•Ligands were discovered that classify patients with systemic lupus erythematosus.•A peptoid binding ELISA had moderate sensitivity and high specificity for lupus.•Peptoid-binding IgG reacts with several disease-associated autoantigens.

Antibodies to a wide range of self-antigens, including those directed against nucleic acids or nucleic acid-binding proteins are the essential biomarkers for diseases such as systemic lupus erythematosus (SLE). Highly complex libraries of nonamers consisting of N-substituted glycines (peptoids) were screened for compounds that bound IgG from patients with SLE and earlier, incomplete autoimmune syndromes. Peptoids were identified that could identify subjects with SLE and related syndromes with a high sensitivity (70%) and specificity (97.5%). Immobilized peptoids were used to isolate IgG from both healthy subjects and SLE patients that reacted with known RNA-binding proteins. In the case of SLE patients, the peptoid-purified IgG reacted with several autoantigens, suggesting that the peptoids are capable of interacting with multiple, structurally similar molecules. These results show that the measurement of IgG binding to peptoids can identify subjects with high levels of pathogenic autoantibodies.