Diagnostic tests for a rare autoimmune disease called anti-phospholipid antibody syndrome (APS) are unreliable, and treatments are not sustainable long-term. However, a new discovery of the disease’s causation from the University of Geneva might alter solutions for both of these problems.
APS is characterized by autoantibodies in the blood plasma that target anticoagulant proteins, leading to excessive blood clotting. Binding of these autoantibodies can occur in the blood vessels and in the placenta, with dangerous consequences such as venous thromboses, strokes, and miscarriages. APS is rare, affecting less than one percent of the population, but this condition often occurs simultaneously with lupus or rheumatoid arthritis.
Current diagnostic approaches for APS require the expertise of a hematologist, an extensive review of a patient’s medical history, and blood tests scanning for three antibodies that indicate APS: anticardiolipin, beta-2 glycoprotein I, lupus anticoagulant. However, variability, specificity, and sensitivity of these tests are not always dependable.
Treatment options for APS almost exclusively involve oral anticoagulants, but extended use raises risk of adverse side effects, especially for pregnant women.
"The current diagnostic tests use the entire protein, which reduces its specificity and leads to standardization issues,” explained Karim Brandt, a researcher from the study. “Consequently, two tests are required at an interval of 12 weeks after a thrombotic episode or following one or more miscarriages. Our new test specifically targets this pathogenic antibody, with rapid and more accurate results."
The new diagnostic approach is to be devised based upon the discovery of the precise location of anti-phospholipid antibody binding. Identifying the exact location of binding allowed scientists to study in detail how the binding occurs and its specific effects on blood clotting. They found that binding triggers the release of pro-inflammatory and pro-thrombotic factors that are the basis of the condition’s dangerous consequences.
"Our breakthrough could also give rise to a targeted treatment that would neutralize specific pathogenic antibodies, reducing not just their actions but also the side effects associated with the current treatment,” Brandt explained. “It would involve injecting the protein motif we have identified into a patient's circulatory system so that it explicitly binds itself to the pathogenic antibody and prevents it from causing harm."
The present study was published in the journal Haematologica.