Phage Immunoprecipitation-Sequencing Reveals CDHR5 Autoantibodies in Select Patients With Interstitial Lung DiseaseVaibhav Upadhyay, Young me Yoon, Sara E. Vazquez, Tania E. Velez, Kirk D. Jones, Cathryn T. Lee, Christopher S. Law, Paul J. Wolters, Seoyeon Lee, Monica M. Yang, Erica Farrand, Imre Noth, Mary E. Strek, Mark S. Anderson, Joseph L. DeRisi, Anne I. Sperling, Anthony K. Shum
American College of Rheumatology, 2024Abstract: Objective: Interstitial lung diseases (ILDs) are a heterogeneous group of disorders that can develop in patients with connective tissue diseases. Establishing autoimmunity in ILD impacts prognosis and treatment. Patients with ILD are screened for autoimmunity by measuring antinuclear autoantibodies, rheumatoid factors, and other nonspecific tests. However, this approach may miss autoimmunity that manifests as autoantibodies to tissue antigens not previously defined in ILD.
Methods: We use Phage Immunoprecipitation-Sequencing (PhIP-Seq) to conduct an autoantibody discovery screen of patients with ILD and controls. We screened for novel autoantigen candidates using PhIP-Seq. We next developed a radio-labeled binding assay and validated the leading candidate in 398 patients with ILD recruited from two academic medical centers and 138 blood bank individuals that formed our reference cohort.
