Serum autoantibodyome reveals that healthy individuals share common autoantibodies

• Published in: Cell reports (Cambridge) Vol. 39; no. 9; p. 110873
• Main Authors: Shome, Mahasish, Chung, Yunro, Chavan, Ramani, Park, Jin G., Qiu, Ji, LaBaer, Joshua
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 31.05.2022
• Subjects: autoantibodies; autoimmunity; biomarker; meta-analysis; protein microarray; meta-analysis; autoimmunity; biomarker; autoantibodies; protein microarray; CP: immunology
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.110873

Autoantibodies are a hallmark of both autoimmune disease and cancer, but they also occur in healthy individuals. Here, we perform a meta-analysis of nine datasets and focus on the common autoantibodies shared by healthy individuals. We report 77 common autoantibodies based on the protein microarray data obtained from probing 182 healthy individual sera on 7,653 human proteins and an additional 90 healthy individual sera on 1,666 human proteins. There is no gender bias; however, the number of autoantibodies increase with age, plateauing around adolescence. We use a bioinformatics pipeline to determine possible molecular-mimicry peptides that can contribute to the elicitation of these common autoantibodies. There is enrichment of intrinsic properties of proteins like hydrophilicity, basicity, aromaticity, and flexibility for common autoantigens. Subcellular localization and tissue-expression analysis reveal that several common autoantigens are sequestered from the circulating autoantibodies. [Display omitted] •Meta-analysis reveals 77 common autoantibodies found in healthy individuals•Autoantibodies in healthy individuals increase with age and then plateau at adolescence•Sequence similarity with viral proteins likely elicits a subset of these antibodies•Several intrinsic properties of common autoantigens are enriched Shome et al. performed a meta-analysis to discover the common autoantibodies found in healthy individuals. These common autoantibodies appear and increase during youth and plateau at adolescence. Bioinformatics techniques demonstrate the potential role of molecular mimicry in their production as well as several common intrinsic biochemical properties.