Novel Technology Identifies Biomarker for Autoimmune Disease

A cutting-edge technology has been developed that can successfully screen human blood for disease markers that may hold the key to better diagnosing and understanding of puzzling health conditions, including autoimmune diseases.

The technology accurately identified human blood markers for neuromyelitis optica (NMO), a rare autoimmune disorder resembling multiple sclerosis that can result in blindness and paralysis, by substituting antibody-binding targets with biologically unnatural molecules called peptoids.

Scientists at Scripps Research Institute (Jupiter, FL, USA) identified several peptoids that bound exclusively to antibodies in NMO patient blood serum and not healthy patients or patients with similar diseases, including multiple sclerosis (MS), lupus, Alzheimer's disease (AD) and narcolepsy. At least one of the peptoids bound to an antibody that is well known to be associated with NMO.

The team used the chemical library screening technology to identify a synthetic peptoid that binds anti-Aquaporin 4 (AQP4) antibodies in the serum of NMO patients. After processing the serum, slides were scanned on a GenePix 4200AL microarray scanner (Molecular Devices; Sunnyvale, CA, USA) by using the 488/635 nm laser at 100% power and a 500-photomultiplier-tube gain.

The investigators screened 100,000 peptoids using a second-generation bead-based screening approach that yielded several peptoid ligands for the antigen-binding site of anti-AQP4 antibodies. They showed in a small preliminary study that the use of a small panel of these peptoids allows one to distinguish between NMO patient serum and serum from healthy controls or patients with MS, AD, narcolepsy, and lupus with high accuracy.

Thomas Kodadek, PhD, the senior author of the study, said, "We find disease biomarkers differently than anyone else. This enables new disease biomarker detection. Additionally, by using these peptoid hits to "fish" for disease-specific antibodies, the system enables disease-specific antibody detection without first knowing the antibodies' natural binding targets." The study was published on March 21, 2013, in the journal Chemistry & Biology.

Related Links:
Scripps Research Institute
Molecular Devices