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

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

Author information

1
Dept. of Pediatric Hematology and Oncology, Justus-Liebig-University, Giessen, Germany.
2
Nuffield Division of Clinical Laboratory Sciences, University of Oxford, Oxford, UK.
3
Dept. of Pediatric Hematology and Oncology, Justus-Liebig-University, Giessen, Germany. Electronic address: Christine.Damm-Welk@paediat.med.uni-giessen.de.

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

PMID:
30077013
DOI:
10.1016/j.clim.2018.07.008
[Indexed for MEDLINE]

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