title: Anti-GalNAcβ: a novel anti-glycan autoantibody associated with pregnancy loss in women with antiphospholipid syndrome and in a mouse experimental model.
abstract: OBJECTIVE
  We evaluated the presence of anti-glycan antibodies (aGA) in patients with antiphospholipid syndrome (APS), and associations between aGA and clinical features of the disease.
  
  
  METHODS
  Sera from APS patients and healthy controls were analyzed for aGA levels by ELISA. Analysis of the association of specific aGA with clinical manifestations of APS was performed. Selected aGA were affinity-purified and injected intravenously into naive mice which were tested for fetal loss. Matrigel invasion assay was performed for detection of choriocarcinoma cells (JAR) invasion and proliferation in the presence of selected aGA. Culture fluid of JAR invasion assays was analyzed for the presence of MMP2 and MMP9.
  
  
  RESULTS
  High levels of several aGA were found in APS sera, of which anti-GalNAc-β was significantly associated with recurrent pregnancy loss. Naive mice infused intravenously with anti-GalNAc-β developed increased fetal loss. Anti-GalNAc-β significantly inhibited the in-vitro percentage of JAR invasiveness and the secretion of MMP2 and MMP9 by human JAR cells.
  
  
  CONCLUSIONS
  APS sera contain significant levels of aGA directed against several glycans. Anti-GalNAc-β Ab is specifically associated with recurrent pregnancy loss both in human patients and experimental mouse model. The pathogenic effects of anti-GalNAc-β include inhibition of JAR cells invasiveness accompanied by decreased MMP2 and MMP9 secretion.
authors.affiliation: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Affiliated to Sackler Faculty of Medicine Tel-Aviv University, Israel.
authors.forename: Miri
authors.initials: M
authors.lastname: Blank
authors.forename: Ilan
authors.initials: I
authors.lastname: Krause
authors.forename: Nir
authors.initials: N
authors.lastname: Dotan
authors.forename: Liat
authors.initials: L
authors.lastname: Anafi
authors.forename: Miriam
authors.initials: M
authors.lastname: Eisenstein
authors.forename: Ricard
authors.initials: R
authors.lastname: Cervera
authors.forename: Pier-Luigi
authors.initials: PL
authors.lastname: Meroni
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Shoenfeld
mesh_terms: D000022:Abortion, Spontaneous / Q000097:blood / Q000276:immunology* / Q000473:pathology; D000818:Animals; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000008:administration & dosage / Q000097:blood / Q000276:immunology*; D001681:Biological Assay; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002822:Choriocarcinoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003094:Collagen; D004195:Disease Models, Animal; D015536:Down-Regulation; D004338:Drug Combinations; D005260:Female; D005685:Galactans / Q000097:blood / Q000276:immunology*; D006801:Humans; D007275:Injections, Intravenous; D007797:Laminin; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D011509:Proteoglycans; D014594:Uterine Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D001323:Autoantibodies; D004338:Drug Combinations; D005685:Galactans; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9