title: Functional autoantibodies against SSX-2 and NY-ESO-1 in multiple myeloma patients after allogeneic stem cell transplantation.
abstract: BACKGROUND
  Multiple myeloma (MM) is the malignancy with the most frequent expression of the highly immunogenic cancer-testis antigens (CTA), and we have performed the first analysis of longitudinal expression, immunological properties, and fine specificity of CTA-specific antibody responses in MM.
  
  
  METHODS
  Frequency and characteristics of antibody responses against cancer-testis antigens MAGE-A3, NY-ESO-1, PRAME, and SSX-2 were analyzed using peripheral blood (N = 1094) and bone marrow (N = 200) plasma samples from 194 MM patients.
  
  
  RESULTS
  We found that antibody responses against CTA were surprisingly rare, only 2.6 and 3.1 % of patients evidenced NY-ESO-1- and SSX-2-specific antibodies, respectively. NY-ESO-1-specific responses were observed during disease progression, while anti-SSX-2 antibodies appeared after allogeneic stem cell transplantation and persisted during clinical remission. We found that NY-ESO-1- and SSX-2-specific antibodies were both capable of activating complement and increasing CTA uptake by antigen-presenting cells. SSX-2-specific antibodies were restricted to IgG3, NY-ESO-1 responses to IgG1 and IgG3. Remarkably, NY-ESO-1-positive sera recognized various non-contiguous regions, while SSX-2-specific responses were directed against a single 6mer epitope, SSX-2(85-90).
  
  
  CONCLUSIONS
  We conclude that primary autoantibodies against intracellular MM-specific tumor antigens SSX-2 and NY-ESO-1 are rare but functional. While their contribution to disease control still remains unclear, our data demonstrate their theoretic ability to affect cellular anti-tumor immunity by formation and uptake of mono- and polyvalent immune complexes.
authors: Department of Internal Medicine II, Oncology/Hematology/Bone Marrow Transplantation with the Section Pneumology, University Cancer Center Hamburg (Hubertus Wald Tumorzentrum), University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors: Tim
authors: T
authors: Luetkens
authors: Sebastian
authors: S
authors: Kobold
authors: Yanran
authors: Y
authors: Cao
authors: Marina
authors: M
authors: Ristic
authors: Georgia
authors: G
authors: Schilling
authors: Sinje
authors: S
authors: Tams
authors: Britta Marlen
authors: BM
authors: Bartels
authors: Julia
authors: J
authors: Templin
authors: Katrin
authors: K
authors: Bartels
authors: York
authors: Y
authors: Hildebrandt
authors: Sara
authors: S
authors: Yousef
authors: Andreas
authors: A
authors: Marx
authors: Friedrich
authors: F
authors: Haag
authors: Carsten
authors: C
authors: Bokemeyer
authors: Nicolaus
authors: N
authors: Kröger
authors: Djordje
authors: D
authors: Atanackovic
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003167:Complement Activation; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D020014:K562 Cells; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology* / Q000628:therapy; D009363:Neoplasm Proteins / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D000951:Antigens, Neoplasm; D001323:Autoantibodies; C104948:CTAG1B protein, human; D000939:Epitopes; C072013:MAGEA3 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C404944:PRAME protein, human; D012097:Repressor Proteins; C093962:synovial sarcoma X breakpoint proteins