Identification of Serum Biomarkers for Systemic Lupus Erythematosus Using a Library of Phage Displayed Random Peptides and Deep Sequencing

Mol Cell Proteomics. 2019 Sep;18(9):1851-1863. doi: 10.1074/mcp.RA119.001582. Epub 2019 Jul 15.

Abstract

Systemic lupus erythematosus (SLE) is one of the most serious autoimmune diseases, characterized by highly diverse clinical manifestations. A biomarker is still needed for accurate diagnostics. SLE serum autoantibodies were discovered and validated using serum samples from independent sample cohorts encompassing 306 participants divided into three groups, i.e. healthy, SLE patients, and other autoimmune-related diseases. To discover biomarkers for SLE, a phage displayed random peptide library (Ph.D. 12) and deep sequencing were applied to screen specific autoantibodies in a total of 100 serum samples from 50 SLE patients and 50 healthy controls. A statistical analysis protocol was set up for the identification of peptides as potential biomarkers. For validation, 10 peptides were analyzed using enzyme-linked immunosorbent assays (ELISA). As a result, four peptides (SLE2018Val001, SLE2018Val002, SLE2018Val006, and SLE2018Val008) were discovered with high diagnostic power to differentiate SLE patients from healthy controls. Among them, two peptides, i.e. SLE2018Val001 and SLE2018Val002, were confirmed between SLE with other autoimmune patients. The procedure we established could be easily adopted for the identification of autoantibodies as biomarkers for many other diseases.

Keywords: Antibodies; Biomarker: Diagnostic; De Novo Sequencing; Peptide Interactions; Phage Display Technologies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Area Under Curve
  • Autoimmune Diseases / blood
  • Biomarkers / blood
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Lupus Erythematosus, Systemic / blood*
  • Male
  • Middle Aged
  • Peptide Library*
  • Peptides / blood*
  • Peptides / genetics
  • Reproducibility of Results

Substances

  • Biomarkers
  • Peptide Library
  • Peptides