Epitope mapping of anti-ALK antibodies in children with anaplastic large cell lymphoma

Clin Immunol. 2018 Oct;195:77-81. doi: 10.1016/j.clim.2018.07.008. Epub 2018 Aug 1.

Abstract

Patients with Nucleophosmin (NPM)-Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) mount ALK autoantibodies. The titer of these autoantibodies inversely correlates with the risk of relapse. The epitopes recognized by these autoantibodies in NPM-ALK might be associated with different ALK-antibody levels. We used overlapping peptide microarray technology to analyze epitope-binding to NPM-ALK by plasma or serum from 129 ALK-positive ALCL patients and 21 controls. Antibodies present in sera from ALCL patients bound to epitopes mainly in the C-terminal region of the ALK portion of NPM-ALK (amino acid positions 469-496, 561-588, 617-644). Patients with higher ALK antibody titers detected the epitope 561-588 more frequently as well as three further epitopes at the N-terminus of the kinase domain compared to patients with intermediate and low titers. These results identify new potential target epitopes for immunotherapy in ALK-positive ALCL. The methodology can be adapted for more reproducible analyses of tumor antigen detection.

Keywords: ALCL; Antibodies; Epitope mapping; Lymphoma; Tumor immunology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Autoantibodies / blood
  • Child
  • Epitope Mapping
  • Epitopes, B-Lymphocyte / genetics
  • Epitopes, B-Lymphocyte / metabolism*
  • Humans
  • Immunotherapy / methods*
  • Lymphoma, Large-Cell, Anaplastic / immunology*
  • Peptides / genetics
  • Peptides / metabolism*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Recurrence
  • Risk

Substances

  • Antigens, Neoplasm
  • Autoantibodies
  • Epitopes, B-Lymphocyte
  • Peptides
  • p80(NPM-ALK) protein
  • Protein-Tyrosine Kinases