Autoimmune antibodies correlate with immune checkpoint therapy-induced toxicities

Proc Natl Acad Sci U S A. 2019 Oct 29;116(44):22246-22251. doi: 10.1073/pnas.1908079116. Epub 2019 Oct 14.

Abstract

Immune checkpoint (IC) therapy provides substantial benefits to cancer patients but can also cause distinctive toxicities termed immune-related adverse events (irAEs). Biomarkers to predict toxicities will be necessary to improve management of patients receiving IC therapy. We relied on serological analysis of recombinant cDNA expression libraries to evaluate plasma samples from patients treated with IC therapy and identified autoantibodies, both in pretreatment and on-treatment samples prior to the development of irAEs, which correlate with the development of immune-related hypophysitis (anti-GNAL and anti-ITM2B autoantibodies) and pneumonitis (anti-CD74 autoantibody). We developed an enzyme-linked immunosorbent assay and tested additional patient samples to confirm our initial findings. Collectively, our data suggest that autoantibodies may correlate with irAEs related to IC therapy, and specific autoantibodies may be detected early for the management of irAEs.

Keywords: autoimmune antibody; hypophysitis; immune checkpoint therapy; immune-related adverse events; pneumonitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / immunology
  • Aged
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Autoantibodies / toxicity
  • Autoimmune Hypophysitis / diagnosis
  • Autoimmune Hypophysitis / etiology*
  • Autoimmune Hypophysitis / immunology
  • Biomarkers / blood
  • Female
  • GTP-Binding Protein alpha Subunits, Gi-Go / immunology
  • Humans
  • Immunotherapy / adverse effects*
  • Male
  • Middle Aged
  • Neoplasms / therapy
  • Pneumonia / etiology*
  • Pneumonia / immunology

Substances

  • Adaptor Proteins, Signal Transducing
  • Autoantibodies
  • Biomarkers
  • ITM2B protein, human
  • GTP-Binding Protein alpha Subunits, Gi-Go