What Is B2 Glycoprotein and Its Role in the Body?

Beta-2 Glycoprotein I (B2GPI) is a protein that circulates in blood plasma. It is also known as Apolipoprotein H (Apo-H), though this name is now considered a misnomer. Produced by the liver and placenta, B2GPI is a normal component of blood with a concentration of about 200 micrograms per milliliter. The protein is composed of five distinct sections, known as domains, which allow it to interact with other substances.

The Normal Function of B2 Glycoprotein

In a healthy individual, Beta-2 Glycoprotein I has a complex regulatory role within the blood clotting system, also known as the coagulation cascade. The protein exhibits both pro-coagulant and anti-coagulant properties, meaning it can promote and inhibit blood clot formation. This dual capability allows it to function as a modulator, helping to maintain balance and prevent excessive clotting.

One of its primary anticoagulant functions is to inhibit parts of the intrinsic coagulation pathway. B2GPI can bind to and inhibit the activation of coagulation Factor XII and prevent the generation of Factor Xa, a component in the clotting process. It also appears to reduce the number of sites on platelets where the prothrombinase complex, which generates thrombin, can form.

Simultaneously, B2GPI can have pro-coagulant effects by interfering with natural anticoagulant pathways, such as inhibiting the activity of activated protein C. This protein is also involved in lipid metabolism, where it binds to negatively charged substances like phospholipids. These are fatty molecules that are part of cell membranes, and this interaction is part of its broader function.

The Immune System and B2 Glycoprotein Antibodies

The immune system can sometimes mistakenly identify the body’s own proteins as foreign threats, producing autoantibodies that attack them. In some individuals, the immune system generates autoantibodies that specifically target B2GPI. These antibodies do not attack the B2GPI protein as it freely circulates in a coiled, circular shape. Instead, they primarily bind to B2GPI after it has attached to a negatively charged surface, like phospholipids on a cell membrane, which causes the protein to change into an open shape.

This binding event is a mechanism in the development of certain autoimmune conditions. When anti-B2GPI antibodies form a complex with the protein, it alters its normal function. Instead of its usual regulatory role, the antibody-B2GPI complex promotes a pro-thrombotic, or pro-clotting, state. This transforms B2GPI from a regulator into a trigger for coagulation.

The exact reason the immune system begins producing these autoantibodies is not fully understood, but it may be induced by factors like infections. An infection can cause a change in the B2GPI protein’s shape, exposing previously hidden parts to the immune system. The resulting antibody-protein complexes can then bind to receptors on cells like platelets and endothelial cells, which line blood vessels. This binding initiates signaling pathways that lead to increased platelet activation and a greater tendency for blood to clot.

Associated Medical Conditions

The persistent presence of anti-B2 glycoprotein antibodies is a characteristic of an autoimmune disorder called Antiphospholipid Syndrome (APS). This condition is identified by two main types of clinical problems: vascular thrombosis and specific pregnancy-related complications. These events are a direct consequence of the pro-clotting state induced by the autoantibodies.

Vascular thrombosis is the formation of blood clots in arteries or veins where they are not supposed to occur. In individuals with APS, this can lead to deep vein thrombosis (DVT) in the legs, or a pulmonary embolism, where a clot travels to the lungs. If a clot forms in an artery, it can block blood flow to the brain, causing a stroke, or to the heart, resulting in a myocardial infarction. These thrombotic events are often unexplained by traditional risk factors.

The second category of complications involves pregnancy. Women with APS may experience recurrent miscarriages, stillbirth, or premature delivery. These adverse outcomes are linked to problems with the placenta, where B2GPI is normally found in significant amounts. The autoantibodies can bind to B2GPI on placental cells called trophoblasts, impairing their function and leading to placental insufficiency or preeclampsia.

Diagnostic Testing and Interpretation

Diagnosing the presence of anti-B2 glycoprotein antibodies is done through a blood test, most commonly an enzyme-linked immunosorbent assay (ELISA). This laboratory test is designed to detect and measure the amount of specific antibodies in a serum sample. Clinicians test for two main classes of anti-B2GPI antibodies: IgG and IgM.

A single positive test result is not sufficient to diagnose Antiphospholipid Syndrome, as these antibodies can appear temporarily due to infections or other causes. To meet the diagnostic criteria for APS, the antibodies must be persistent. This is confirmed by repeating the blood test and finding a moderate to high level of the antibodies on two or more occasions, with the tests spaced at least 12 weeks apart.

The interpretation of test results requires a healthcare provider. The presence of persistent anti-B2GPI antibodies, especially IgG, is one of three main laboratory criteria for APS, alongside tests for lupus anticoagulant and anticardiolipin antibodies. A diagnosis is made when a patient has at least one positive lab finding combined with a clinical history of vascular thrombosis or pregnancy complications. The level and type of antibody can also provide information about the risk for future complications.