title: The thrombophilic network of autoantibodies in celiac disease.
abstract: BACKGROUND
  Celiac disease is a life-long autoimmune condition, affecting genetically susceptible individuals that may present with thromboembolic phenomena. This thrombophilia represents a puzzle with multiple constituents: hyperhomocysteinemia, B12 and\or folate deficiency, methylenetetrahydrofolate reductase mutations, and protein C and S deficiency due to vitamin K deficiency. However, the well known thrombogenic factors, antiphosphatidylserine/prothrombin and antiprothrombin have never been explored in celiac disease.
  
  
  METHODS
  The serum autoantibody levels were determined in 248 individuals, classified into three groups. Group 1 comprised 70 children with definitive celiac disease (age: 7.04 ±4.3 years, male to female ratio 1.06) and group 2 comprised 88 normal children (age: 6.7 ±4.17 years, male to female ratio 0.87), representing controls. The pediatric populations were compared to group 3, which included 90 adults who were family members (parents) of group 1 (age: 34.6 ±11.35 years, male to female ratio 1.2). Antibodies were checked by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Mean optical density levels of serum antiphosphatidylserine/prothrombin immunoglobulin G antibodies were 32.4 ±19.4, 3.6 ±2.5 and 16.1 ±15.8 absorbance units in groups 1, 2 and 3 respectively (P <0.0001), with 45.7%, 0% and 7.8% of groups 1, 2 and 3 respectively positive for the antibody (P <0.01). Mean optical density levels of serum antiphosphatidylserine/prothrombin immunoglobulin M antibodies were 14.2 ±8.7, 6.7 ±6.4 and 12.4 ±15.5 absorbance units in groups 1, 2 and 3 respectively (P <0.0001), with 7.1%, 3.4% and 9.9% of groups 1, 2 and 3 positive for the antibody. Mean optical density levels of serum antiprothrombin and antiphospholipid immunoglobulin G antibodies were higher in groups 1 and 3 compared with 2 (P <0.005) and in groups 1 and 2 compared with 3 (P <0.01), respectively. Groups 1, 2 and 3 were positive for antiphospholipid immunoglobulin G antibodies (groups 1 and 2 compared with 3) . Celiac disease sera harbor a higher antiprothrombin immunoglobulin G level compared with controls.
  
  
  CONCLUSIONS
  It is suggested that the intestinal injury, endothelial dysfunction, platelet abnormality and enhanced apoptosis recently described in celiac disease are at the origin of the increased exposure of phospholipids or new epitopes representing autoantigens. Those autoantibodies might play a pathogenic role in the thrombophilia associated with celiac disease and represent markers for potential anticoagulant preventive therapy.
authors.affiliation: Pediatric Gastroenterology and Nutrition Unit, Carmel Medical Center, B, Rappaport School of Medicine, Technion-Israel institute of Technology, Michal St, No 7, Haifa, 34362, Israel. lerner_aaron@clalit.org.il
authors.forename: Aaron
authors.initials: A
authors.lastname: Lerner
authors.forename: Nancy
authors.initials: N
authors.lastname: Agmon-Levin
authors.forename: Yinon
authors.initials: Y
authors.lastname: Shapira
authors.forename: Boris
authors.initials: B
authors.lastname: Gilburd
authors.forename: Sandra
authors.initials: S
authors.lastname: Reuter
authors.forename: Idit
authors.initials: I
authors.lastname: Lavi
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Shoenfeld
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology*; D002446:Celiac Disease / Q000150:complications* / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019851:Thrombophilia / Q000209:etiology* / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies
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