title: Antibody binding to megakaryocytes in vivo in patients with immune thrombocytopenia.
abstract: OBJECTIVE
  Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder caused by increased platelet destruction and impaired platelet production. Antibody binding to megakaryocytes may occur in ITP, but in vivo evidence of this phenomenon is lacking.
  
  
  METHODS
  We determined the proportion of megakaryocytes bound with immunoglobulin G (IgG) in bone marrow samples from primary patients with ITP (n = 17), normal controls (n = 13) and thrombocytopenic patients with myelodysplastic syndrome (MDS; n = 10). Serial histological sections from archived bone marrow biopsies were stained for CD61 and IgG. IgG binding and the number of bone marrow megakaryocytes were determined morphologically by a hematopathologist with four assessors after a calibration exercise to ensure consistency.
  
  
  RESULTS
  The proportion of ITP patients with high IgG binding (>50% of bone marrow megakaryocytes) was increased compared with normal controls [12/17 (71%) vs. 3/13 (23%), P = 0.03]. However, the proportion of ITP patients with high IgG binding was no different than thrombocytopenic patients with MDS [12/17 (71%) vs. 7/10 (70%), P = 1.00]. IgG binding was associated with increased megakaryocyte numbers. Like platelet-associated IgG, megakaryocyte-associated IgG is related to thrombocytopenia but may not be specific for ITP.
  
  
  CONCLUSIONS
  Mechanistic studies in ITP should focus on antibody specificity and include thrombocytopenic control patients.
authors: Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.|Canadian Blood Services, Hamilton, Ontario, Canada.
authors: Donald M
authors: DM
authors: Arnold
authors: Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Ishac
authors: I
authors: Nazi
authors: Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Lisa J
authors: LJ
authors: Toltl
authors: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Catherine
authors: C
authors: Ross
authors: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors: Nikola
authors: N
authors: Ivetic
authors: Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: James W
authors: JW
authors: Smith
authors: Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Yang
authors: Y
authors: Liu
authors: Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: John G
authors: JG
authors: Kelton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000276:immunology* / Q000378:metabolism*; D001324:Autoantigens / Q000276:immunology; D001706:Biopsy; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism; D001853:Bone Marrow / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D008533:Megakaryocytes / Q000276:immunology* / Q000378:metabolism*; D008875:Middle Aged; D010976:Platelet Count; D011485:Protein Binding; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G
keywords: antibody specificity; autoimmune thrombocytopenia; blood platelet disorders; megakaryocytes