title: Patients with multiple myeloma develop SOX2-specific autoantibodies after allogeneic stem cell transplantation.
abstract: The occurrence of SOX2-specific autoantibodies seems to be associated with an improved prognosis in patients with monoclonal gammopathy of undetermined significance (MGUS). However, it is unclear if SOX2-specific antibodies also develop in established multiple myeloma (MM). Screening 1094 peripheral blood (PB) sera from 196 MM patients and 100 PB sera from healthy donors, we detected SOX2-specific autoantibodies in 7.7% and 2.0% of patients and donors, respectively. We identified SOX2(211-230) as an immunodominant antibody-epitope within the full protein sequence. SOX2 antigen was expressed in most healthy tissues and its expression did not correlate with the number of BM-resident plasma cells. Accordingly, anti-SOX2 immunity was not related to SOX2 expression levels or tumor burden in the patients' BM. The only clinical factor predicting the development of anti-SOX2 immunity was application of allogeneic stem cell transplantation (alloSCT). Anti-SOX2 antibodies occurred more frequently in patients who had received alloSCT (n = 74). Moreover, most SOX2-seropositive patients had only developed antibodies after alloSCT. This finding indicates that alloSCT is able to break tolerance towards this commonly expressed antigen. The questions whether SOX2-specific autoantibodies merely represent an epiphenomenon, are related to graft-versus-host effects or participate in the immune control of myeloma needs to be answered in prospective studies.
authors.affiliation: Department of Internal Medicine II, Oncology/Hematology/Bone Marrow Transplantation with the Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. sebastian.kobold@hotmail.de
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kobold
authors.forename: Sinje
authors.initials: S
authors.lastname: Tams
authors.forename: Tim
authors.initials: T
authors.lastname: Luetkens
authors.forename: Yanran
authors.initials: Y
authors.lastname: Cao
authors.forename: Orhan
authors.initials: O
authors.lastname: Sezer
authors.forename: Britta Marlen
authors.initials: BM
authors.lastname: Bartels
authors.forename: Henrike
authors.initials: H
authors.lastname: Reinhard
authors.forename: Julia
authors.initials: J
authors.lastname: Templin
authors.forename: Katrin
authors.initials: K
authors.lastname: Bartels
authors.forename: York
authors.initials: Y
authors.lastname: Hildebrandt
authors.forename: Nesrine
authors.initials: N
authors.lastname: Lajmi
authors.forename: Andreas
authors.initials: A
authors.lastname: Marx
authors.forename: Friedrich
authors.initials: F
authors.lastname: Haag
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.forename: Djordje
authors.initials: D
authors.lastname: Atanackovic
mesh_terms: D000918:Antibody Specificity / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D045744:Cell Line, Tumor; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D009101:Multiple Myeloma / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D011379:Prognosis; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors