title: Antigen-specificity of oligoclonal abnormal protein bands in multiple myeloma after allogeneic stem cell transplantation.
abstract: Myeloma patients may develop oligoclonal immunoglobulins, so-called abnormal protein bands (APB), after stem cell transplantation. APB do not correspond to the patient's paraprotein and confer a good prognosis. We set out to investigate whether such APB represent a humoral anti-myeloma immune response by screening immunoglobulins of 15 myeloma patients after allogeneic stem cell transplantation and a control group of healthy donors for reactivity with myeloma protein extracts. While the immunoglobulins of healthy donors did not react with myeloma protein extracts, patient-derived immunoglobulins showed variable levels of interaction, depending on the presence of APB on immunofixation. Most commonly, we detected interactions with heat-shock proteins, followed by neutral alpha-glucosidase, alpha-enolase and vimentin, as well as proliferating cell nuclear antigen and MAGEA4. More than 80% of targets were upregulated in myeloma. Heat-shock protein 60 (HSP60) was subsequently evaluated as an exemplary antigen. We found that HSP60 was aberrantly displayed on the surface of primary myeloma cells. Indeed, patient-derived APB-containing immunoglobulins recognized surface HSP60 suggesting that this antigen becomes accessible to the immune system after aberrant membrane exposition. We conclude that immunoglobulin fractions with APB recognize recurrent myeloma antigens and that this humoral response may contribute to the more favorable prognosis in patients with APB.
authors.affiliation: Department of Oncology and Hematology, BMT with Section Pneumology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hubertus Wald Tumorzentrum, Martinistrasse 52, 20246 Hamburg, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Rahlff
authors.forename: Maria
authors.initials: M
authors.lastname: Trusch
authors.forename: Friedrich
authors.initials: F
authors.lastname: Haag
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bacher
authors.forename: Andrea
authors.initials: A
authors.lastname: Horst
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schlüter
authors.forename: Mascha
authors.initials: M
authors.lastname: Binder
mesh_terms: D000951:Antigens, Neoplasm / Q000097:blood / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology*; D018834:Chaperonin 60 / Q000097:blood / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000097:blood / Q000276:immunology; D024101:Mitochondrial Proteins / Q000097:blood / Q000276:immunology*; D009101:Multiple Myeloma / Q000276:immunology*; D009363:Neoplasm Proteins / Q000097:blood / Q000276:immunology; D010751:Phosphopyruvate Hydratase / Q000097:blood / Q000276:immunology; D018809:Proliferating Cell Nuclear Antigen / Q000097:blood / Q000276:immunology; D033581:Stem Cell Transplantation; D015854:Up-Regulation; D014746:Vimentin / Q000097:blood / Q000276:immunology; D000520:alpha-Glucosidases / Q000097:blood / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D018834:Chaperonin 60; C060293:HSPD1 protein, human; D007136:Immunoglobulins; C095204:MAGEA4 protein, human; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen; D014746:Vimentin; D000520:alpha-Glucosidases; D010751:Phosphopyruvate Hydratase