title: ABO blood group IgM isoagglutinins interact with tumor-associated O-glycan structures in pancreatic cancer.
abstract: OBJECTIVE
  The ABO gene locus is associated with the risk of developing pancreatic ductal adenocarcinoma (PDAC) resulting in an increased incidence in individuals with non-O blood groups. Up to 90% of PDAC specimens display alterations in mucin type O-GalNAc glycosylation. Because aberrant O-GalNAc glycans (Tn and T antigen) are structurally related to blood group A and B glycans, we investigated the role of IgM isoagglutinins in PDAC.
  
  
  METHODS
  Binding studies of IgM isoagglutinins toward blood group A, B, Tn antigen, and T antigen glycoconjugates from patients with PDAC and healthy individuals were conducted. Isoagglutinin titers and total IgM were compared between patients with PDAC and control group. An anti-A antibody was used for immunoprecipitation of aberrant O-glycosylated tumor proteins and subsequent mass spectromic analysis.
  
  
  RESULTS
  We found that IgM isoagglutinins bind blood group antigens, Tn and T glycoconjugates as well as tumor-derived glycoproteins. Blood group A isoagglutinins exhibited a strong binding toward blood group B antigen and T antigen, whereas blood group B showed binding to blood group A antigen and Tn antigen. Furthermore, we confirmed a decreased frequency in individuals with blood group O and observed a significant decrease of IgM isoagglutinin titers in PDAC sera compared with control sera, whereas total IgM levels were unaltered. We identified new PDAC-derived O-GalNAc glycoproteins by mass spectrometry using a blood group A-specific antibody.
  
  
  CONCLUSIONS
  Our data elucidated a novel interaction of blood group IgM isoagglutinins and PDAC O-GalNAc glycoproteins that may contribute to the pathogenesis and progression of pancreatic cancer.
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Bianca T
authors.initials: BT
authors.lastname: Hofmann
authors.affiliation: Department of Clinical Chemistry, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Stehr
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Dohrmann
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Cenap
authors.initials: C
authors.lastname: Güngör
authors.affiliation: Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Insitute of Medical Statistics, Informatics and Epidemiology (IMSIE) University Hospital of Cologne, Cologne, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Herich
authors.affiliation: Department of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Hiller
authors.affiliation: Department of Clinical Chemistry, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Sönke
authors.initials: S
authors.lastname: Harder
authors.affiliation: Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Ewald
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Gebauer
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Tachezy
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Clarissa
authors.initials: C
authors.lastname: Precht
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Bockhorn
authors.affiliation: Department of Clinical Chemistry, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wagener
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. ge.wolters@uke.de.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Wolters-Eisfeld
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology; D000328:Adult; D000368:Aged; D000373:Agglutinins / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011134:Polysaccharides / Q000378:metabolism*; D011485:Protein Binding; D055815:Young Adult
chemical_list: D000017:ABO Blood-Group System; D000373:Agglutinins; D007075:Immunoglobulin M; D011134:Polysaccharides