Antibody binding to megakaryocytes in vivo in patients with immune thrombocytopenia

Eur J Haematol. 2015 Dec;95(6):532-7. doi: 10.1111/ejh.12528. Epub 2015 Mar 13.

Abstract

Objectives: 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.

Conclusion: Mechanistic studies in ITP should focus on antibody specificity and include thrombocytopenic control patients.

Keywords: antibody specificity; autoimmune thrombocytopenia; blood platelet disorders; megakaryocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies / immunology*
  • Autoantibodies / metabolism*
  • Autoantigens / immunology
  • Biopsy
  • Blood Platelets / immunology
  • Blood Platelets / metabolism
  • Bone Marrow / pathology
  • Case-Control Studies
  • Female
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin G / metabolism
  • Leukocyte Count
  • Male
  • Megakaryocytes / immunology*
  • Megakaryocytes / metabolism*
  • Middle Aged
  • Platelet Count
  • Protein Binding
  • Purpura, Thrombocytopenic, Idiopathic / immunology*
  • Purpura, Thrombocytopenic, Idiopathic / metabolism*
  • Purpura, Thrombocytopenic, Idiopathic / pathology

Substances

  • Autoantibodies
  • Autoantigens
  • Immunoglobulin G