038 Autoantibody landscape of cutaneous disorders revealed by wet protein array

      Autoantibodies are found in various pathological conditions such as autoimmune diseases, infectious diseases, and malignant tumors. However, their clinical implications have not yet been fully elucidated. Herein, we employed our proteome-wide cDNA library (HuPEX) which covers approximately 90% of the human transcriptome for proteome-wide autoantibody evaluation. In the first step, proteome-wide autoantibody screening was conducted upon pooled serum. In the second step, the concentration of selected autoantibodies within individual sera was quantified. Primary screening identified a total of 565 autoantibodies in three representative inflammatory disorders: systemic sclerosis (SSc), psoriasis, and cutaneous arteritis. Quantitative analysis revealed that each autoantibody level either positively or negatively correlated with serum levels of C-reactive protein. In SSc, we discovered 18 autoantibodies whose serum levels positively correlated with serum levels of C-reactive protein. Enrichment analysis revealed that significantly high proportion of the proteins targeted by these 18 autoantibodies was regulated by SNAI1, a transcription factor known to be upregulated in SSc skin. Sum of these autoantibodies was significantly associated with the clinical manifestations of SSc. Similar results were obtained for psoriasis and cutaneous arteritis. In addition, 488 autoantibodies were detected from the sera of malignant melanoma. Notably, patients with metastases had increased overall autoantibody production compared to those with tumors limiting to the primary site. Collectively, our novel technology can reveal the “autoantibody landscape” of human subjects and may provide novel clinical biomarkers.