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

Publication date: Available online 1 August 2018

Source: Clinical Immunology

Author(s): Fabian Knörr, Simone Weber, Vijay K. Singh, Karen Pulford, Alfred Reiter, Wilhelm Woessmann, Christine Damm-Welk

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.

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