Autoantibody Landscape Revealed by Wet Protein Array: Sum of Autoantibody Levels Reflects Disease Status

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 conducted proteome-wide autoantibody screening and quantification with wet protein arrays consisting of proteins synthesized from proteome-wide human cDNA library (HuPEX) maintaining their three-dimensional structure. A total of 565 autoantibodies were identified from the sera of three representative inflammatory disorders (systemic sclerosis, psoriasis, and cutaneous arteritis). Each autoantibody level either positively or negatively correlated with serum levels of C-reactive protein, the best-recognized indicator of inflammation. In particular, we discovered total levels of a subset of autoantibodies correlates with the severity of clinical symptoms. From the sera of malignant melanoma, 488 autoantibodies were detected. Notably, patients with metastases had increased overall autoantibody production compared to those with tumors limiting to the primary site. Collectively, proteome-wide screening of autoantibodies using the in vitro proteome can reveal the autoantibody landscape of human subjects and may provide novel clinical biomarkers.

Automated summary

Autoantibodies were detected in various pathological conditions using wet protein arrays synthesized from a proteome-wide human cDNA library, showing correlation with C-reactive protein levels and clinical symptoms severity. Patients with metastatic malignant melanoma had increased overall production of autoantibodies compared to those with primary tumors. This proteome-wide screening may offer novel clinical biomarkers.