PhIP-Seq characterization of autoantibodies from patients with multiple sclerosis, type 1 diabetes and rheumatoid arthritis

J Autoimmun. 2013 Jun;43:1-9. doi: 10.1016/j.jaut.2013.01.013. Epub 2013 Mar 13.

Abstract

Autoimmune disease results from a loss of tolerance to self-antigens in genetically susceptible individuals. Completely understanding this process requires that targeted antigens be identified, and so a number of techniques have been developed to determine immune receptor specificities. We previously reported the construction of a phage-displayed synthetic human peptidome and a proof-of-principle analysis of antibodies from three patients with neurological autoimmunity. Here we present data from a large-scale screen of 298 independent antibody repertoires, including those from 73 healthy sera, using phage immunoprecipitation sequencing. The resulting database of peptide-antibody interactions characterizes each individual's unique autoantibody fingerprint, and includes specificities found to occur frequently in the general population as well as those associated with disease. Screening type 1 diabetes (T1D) patients revealed a prematurely polyautoreactive phenotype compared with their matched controls. A collection of cerebrospinal fluids and sera from 63 multiple sclerosis patients uncovered novel, as well as previously reported antibody-peptide interactions. Finally, a screen of synovial fluids and sera from 64 rheumatoid arthritis patients revealed novel disease-associated antibody specificities that were independent of seropositivity status. This work demonstrates the utility of performing PhIP-Seq screens on large numbers of individuals and is another step toward defining the full complement of autoimmunoreactivities in health and disease.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Antibody Specificity
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology*
  • Autoantibodies / blood*
  • Autoantibodies / cerebrospinal fluid*
  • Autoantigens / genetics
  • Autoantigens / immunology
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • High-Throughput Screening Assays
  • Humans
  • Male
  • Molecular Sequence Data
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / immunology*
  • Peptide Library
  • Young Adult

Substances

  • Autoantibodies
  • Autoantigens
  • Peptide Library