title: Humoral immune responses against the immature laminin receptor protein show prognostic significance in patients with chronic lymphocytic leukemia.
abstract: 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 cytotoxicity assays. In the analysis of 11 CLL patients after allogeneic hematopoietic 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.
authors.affiliation: Department of Hematology and Stem Cell Transplantation, Asklepios Hospital St. Georg, Lohmühlenstrasse 5, Hamburg, Germany.
authors.forename: Birte
authors.initials: B
authors.lastname: Friedrichs
authors.forename: Sandra
authors.initials: S
authors.lastname: Siegel
authors.forename: Marita
authors.initials: M
authors.lastname: Kloess
authors.forename: Adel
authors.initials: A
authors.lastname: Barsoum
authors.forename: Joseph
authors.initials: J
authors.lastname: Coggin
authors.forename: James
authors.initials: J
authors.lastname: Rohrer
authors.forename: Ilja
authors.initials: I
authors.lastname: Jakob
authors.forename: Markus
authors.initials: M
authors.lastname: Tiemann
authors.forename: Klaus
authors.initials: K
authors.lastname: Heidorn
authors.forename: Christoph
authors.initials: C
authors.lastname: Schulte
authors.forename: Dieter
authors.initials: D
authors.lastname: Kabelitz
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinmann
authors.forename: Norbert
authors.initials: N
authors.lastname: Schmitz
authors.forename: Matthias
authors.initials: M
authors.lastname: Zeis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000912:Antibodies, Neoplasm / Q000097:blood* / Q000276:immunology; D000917:Antibody Formation; D000918:Antibody Specificity / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D018572:Disease-Free Survival; D005260:Female; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000276:immunology / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D017474:Receptors, Laminin / Q000276:immunology*; D012269:Ribosomal Proteins / Q000276:immunology*; D015996:Survival Rate; D014184:Transplantation, Homologous
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D007074:Immunoglobulin G; C510624:RPSA protein, human; D017474:Receptors, Laminin; D012269:Ribosomal Proteins; C031192:oncofetal antigens