Antiplatelet antibodies in WASP(-) mice correlate with evidence of increased in vivo platelet consumption.

Abstract

OBJECTIVE:

To study the role of antiplatelet antibodies in the thrombocytopenia of murine Wiskott-Aldrich syndrome (WAS).

MATERIALS AND METHODS:

A flow cytometric method was developed for detection of serum antiplatelet antibodies via their binding to intact target platelets lacking surface antibodies. Platelets were labeled with 5-chloromethylfluorescein diacetate (CMFDA) in order to track their clearance from the circulation. WASP(-)muMT(-/-) mice were generated by standard breeding methods.

RESULTS:

Serum antiplatelet antibodies were detected in approximately 40% of WASP(-) males. The mean level of reticulated platelets is significantly increased in these antibody(+) males. While WASP(-) males show an approximately 50% reduction in platelet counts, 5% to 10% show a more severe thrombocytopenia associated with increased reticulated platelets, suggesting the presence of clearance-inducing antiplatelet antibodies. In support of that inference, 90% of the latter mice show detectable serum antiplatelet antibodies. The antibodies are primarily immunoglobulin G, and are also detected in >30% of CD47(-/-) males. WASP(-)muMT(-/-) males, which demonstrate no serum- or platelet-associated antibodies, show a degree of thrombocytopenia similar to that of WASP(-) males. Their platelet clearance rates remain accelerated--more so in WASP(-)muMT(-/-) than WASP(+)muMT(-/-) recipients.

CONCLUSIONS:

These findings suggest that platelet WASP deficiency results in an increase in platelet clearance rates by two mechanisms: an antibody-independent mechanism that largely requires WASP deficiency in trans, and an antibody-dependent mechanism that does not. Both an increased incidence of antiplatelet antibodies and an increased susceptibility to their effects contribute to antibody-dependent clearance of WASP(-) platelets.

• Authors: Bindumadhav M Marathe, Amanda Prislovsky, Alexander Astrakhan, David J Rawlings, Jim Y Wan, Ted S Strom
• Journal: Experimental hematology (Exp Hematol) Vol. 37 Issue 11 Pg. 1353-63 (Nov 2009) ISSN: 1873-2399 [Electronic] Netherlands
• PMID: 19733207 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Autoantibodies
• CD47 Antigen
• Cd47 protein, mouse
• Opsonin Proteins
• Was protein, mouse
• Wiskott-Aldrich Syndrome Protein

Topics

• Animals
• Autoantibodies (immunology)
• Autoimmune Diseases (blood, genetics, immunology, pathology)
• Blood Platelets (immunology)
• Bone Marrow (pathology)
• CD47 Antigen (genetics, physiology)
• Male
• Mice
• Mice, Knockout
• Models, Animal
• Opsonin Proteins (immunology)
• Phagocytosis (immunology, physiology)
• Platelet Count
• Spleen (pathology)
• Splenomegaly (etiology, pathology)
• Wiskott-Aldrich Syndrome (blood, genetics, immunology, pathology)
• Wiskott-Aldrich Syndrome Protein (deficiency)