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* Department of Hematology and Stem Cell Transplantation, Asklepios Hospital St. Georg;
Institute for Hematopathology, Hamburg;
Institute for Medical Informatics, Statistics and Epidemiology, University Leipzig, Leipzig;
Institute of Immunology, University of Kiel, Kiel, Germany; and
¶ Department of Microbiology and Immunology, University of South Alabama College of Medicine, Mobile, AL 36688
Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course. The role of an autologous tumor-specific immune control contributing to the variable length of survival in CLL is poorly understood. We investigated whether humoral immunity specific for the CLL-associated Ag oncofetal Ag/immature laminin receptor (OFA/iLR) has a prognostic value in CLL. Among sera of 67 untreated patients with CLL, 23 (34.3%) had detectable OFA/iLR Abs that were reactive for at least one specific OFA/iLR epitope. Patients with humoral responses compared with patients with nonreactive sera had a longer progression-free survival (p = 0.029). IgG subclass analyses showed a predominant IgG1 and IgG3 response. OFA/iLR Abs were capable of recognizing and selectively killing OFA/iLR-expressing CLL cells in complement-mediated and Ab-dependent cellular cytotoxi cityassays. In the analysis of 11 CLL patients after allogeneic hematopoetic stem cell transplantation, 8 showed high values for OFA/iLR Abs that specifically recognized the extracellular domain of the protein, suggesting a potential role of anti-OFA/iLR-directed immune responses to the graft-vs-leukemia effect in CLL. Our data suggest that spontaneous tumor-specific humoral immune responses against OFA/iLR exist in a significant proportion of CLL patients and that superior progression-free survival in those patients could reflect autologous immune control.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by the Deutsche Forschungsgemeinschaft ZE 697/2-1 grant and in part by the Erich und Gertrud Roggenbuck-Stiftung grant.
2 B.F. performed research, analyzed data, and wrote the manuscript. S.S. performed research and wrote the manuscript. M.K. performed statistical analysis, A.D. contributed vital new reagents, J.C. provided vital new reagents, J.R. provided vital new reagents, I.J. performed research, M.T. performed research, K.H. performed research, C.S. performed research, D.K. analyzed data, J.S. designed research, N.S. analyzed and interpreted data, and M.Z. designed research and drafted the manuscript.
3 B.F. and S.S. contributed equally to this work.
4 Address correspondence and reprint requests to Dr. Matthias Zeis, Department of Hematology, Asklepios Hospital St. Georg, Lohmühlenstrasse 5, 20099 Hamburg, Germany. E-mail address: mzeis47{at}hotmail.com
5 Abbreviations used in this paper: CLL, chronic lymphocytic leukemia; OFA/iLR, oncofetal Ag/immature laminin receptor; FISH, fluorescence in situ hybridization; ADCC, Ab-dependent cellular cytotoxicity; PFS, progression-free survival; allo-SCT, allogeneic stem cell transplantation; CDC, complement-dependent cytotoxicity.
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