Identification of anti-moesin antibodies in the serums of patients with antiphospholipid syndrome

Thromb Res. 2015 May;135(5):867-72. doi: 10.1016/j.thromres.2015.02.018. Epub 2015 Feb 25.

Abstract

Introduction: The antiphospholipid syndrome (APS) is an acquired autoimmune disease characterized by recurrent vascular thrombosis and obstetric complications. However, the precise mechanisms by which the autoantibodies mediate disease remain to be elucidated. Moesin is an intracellular protein that links the cell membrane and cytoskeleton, mediating the formation of microtubules and cell adhesion sites as well as ruffling of the cell membrane, which is crucial for platelet activation.

Materials and methods: We screened the serums from patients with APS for the presence of anti-moesin antibodies (anti-moesin Abs) recognizing antigens derived from prokaryotic expression system, and investigated the effect of murine monoclonal anti-moesin Abs (anti-moesin mAbs) on platelet activation and aggregation by flow cytometry and platelet aggregation assay in vitro to study their potential pathogenic role in APS.

Results: The presence of anti-amino (N)-terminal portion of moesin antibodies (anti-moesin-N Abs) was observed in 73% (73/100) patients with APS, which was significantly higher than anti-cardiolipin antibodies (aCL, 49%) and anti-β2 glycoprotein I antibodies (anti-β2GPI, 43%). Moreover, the elevated anti-moesin-N Abs levels significantly correlated with plasma levels of anti-β2GPI (rs=0.474, P<0.001) rather than aCL (P=0.203). The murine anti-moesin mAbs promote platelet activation and aggregation in vitro, which could be effectively neutralized by moesin-N.

Conclusions: In combination of the detection of aCL and anti-β2GPI, screening for the presence of anti-moesin-N Abs might has its value in facilitating the laboratory diagnosis of APS. The pathogenic role of anti-moesin-N Abs in the serums of APS patients needs to be further studied.

Keywords: Antiphospholipid Syndrome; Autoantibody; Moesin; Platelet Activation.

MeSH terms

  • Animals
  • Antibodies, Anticardiolipin / blood
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Neutralizing / immunology
  • Antibody Specificity
  • Antiphospholipid Syndrome / blood*
  • Antiphospholipid Syndrome / immunology
  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Autoantigens / immunology*
  • DNA, Complementary / genetics
  • Female
  • Humans
  • Hybridomas / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microfilament Proteins / genetics
  • Microfilament Proteins / immunology*
  • Platelet Activation / drug effects
  • Platelet Activation / immunology
  • Platelet Aggregation / drug effects
  • Platelet Aggregation / immunology
  • Pregnancy
  • Pregnancy Complications / blood
  • Pregnancy Complications / immunology
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / immunology
  • beta 2-Glycoprotein I / immunology

Substances

  • Antibodies, Anticardiolipin
  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Autoantibodies
  • Autoantigens
  • DNA, Complementary
  • Microfilament Proteins
  • Recombinant Fusion Proteins
  • beta 2-Glycoprotein I
  • moesin