Fundamentals in Understanding the Immunology of ITP

Antibodies are IgG molecules with the structure shown.

The molecule consists of 2 Heavy chains labeled H on the diagram and 2 light chains labeled L on the diagram.

There are two important regions of the IgG molecule.

The Fab portion binds with the antigen. In the Case of WinRho^®SDF which is an IgG, the antigen to which the Fab portion of the IgG binds is the D antigen of the Rh factor of the Red Blood Cells.

The Fc portion of the molecule binds with Fc receptors (FcR) found in the reticuloendothelial system (chiefly macrophages of spleen).

Diseases may cause the production of Antibodies

With Viral Infections, IgM and IgA antibodies are first produced. After a period of time (usually 7-10 days) IgG starts to be produced. IgG antibodies provide long term immunity (lifelong in some cases) to that virus or other antigen.

IgG antibodies can be produced under other clinical situations such as pregnancy (as in hemolytic disease of newborn (HDN) and in allo-immune thrombocytopenia).

Pathophysiology

Pathogenesis of ITP

• Poorly understood
• Platelets are coated with autoantibody or immune complexes. They are then transported to the Reticulo Endothelial System (RES) where the platelets are destroyed.
• Megakaryocytes are often but may be
• Production of platelets is usually or normal
• Thrombocytopenia is most problematic when platelets <20 x 10⁹/L

Molecular Mimicry Binding of Antibodies to a Platelet in ITP

Molecular Mimicry is the term used to describe the process whereby IgG antibodies generated against a viral infection can also become attached to a tissue or cell type of the body such as platelets in the case of ITP, or the collagen of joints in rheumatoid arthritis.

Opsonization is the process whereby an antibody attached to a virus, bacteria or cell type renders that virus, bacteria or cell type susceptible to phagocytosis. Platelets that become opsonized by IgG antibodies in ITP will undergo phagocytosis and will be destroyed.

The spleen and the reticuloendothelial system (RES) are the components of the immune system responsible for removal of opsonized platelets.

Approximately 80% of the opsonized platelets are removed by the spleen which is the reason splenectomy may be an effective treatment of ITP in some cases. The Fc portion of the IgG molecule binds to receptors (Fc receptors or Fc R) in the macrophages of the Reticulo Endothelial System (RES).