Antiphospholipid syndrome (APS) is an autoimmune disorder where the immune system mistakenly creates specific antibodies, known as antiphospholipid antibodies (aPL). These antibodies target proteins bound to fat molecules, causing the blood to become prone to clotting in both arteries and veins (thrombophilia). Blood clots can lead to serious complications such as stroke, heart attack, and deep vein thrombosis. Women with APS also face increased risks of pregnancy complications, including recurrent miscarriages and premature delivery.
Is APS Directly Inherited?
Antiphospholipid Syndrome is not classified as a classic hereditary disorder passed directly from parent to child through a single gene. Most cases of APS are sporadic, meaning they occur in individuals with no prior family history. The condition is fundamentally an acquired autoimmune disease, not an inherited trait. It is important to distinguish between inheriting the disease itself and inheriting a predisposition to developing the condition.
The Role of Genetic Predisposition
While APS is not directly inherited, it does show a tendency to run in families, pointing to a genetic susceptibility. Certain gene variations can increase an individual’s likelihood of developing the autoimmune response, but they do not guarantee the disease. The strongest genetic link is found within the Human Leukocyte Antigen (HLA) system, which regulates the immune response.
Variations in specific HLA class II alleles, such as HLA-DR4 and HLA-DR7, are associated with a higher risk of producing antiphospholipid antibodies. These variants affect how the immune system presents antigens, making an individual more prone to mistakenly attacking their own proteins. Other genes involved in immune system signaling and blood clotting also contribute to the overall risk. This complex interaction suggests that APS is a polygenic disease, where multiple genetic factors combine to increase susceptibility.
Non-Genetic Factors in Disease Development
Genetic predisposition alone is usually not enough to cause Antiphospholipid Syndrome. The onset of the disease often requires a non-genetic, or environmental, trigger to activate the autoimmune response in a susceptible individual. This is sometimes described by the “two-hit” theory, where underlying genetic risk combines with a second factor to incite the thrombotic effects.
Infectious agents are strongly implicated as common triggers, particularly certain viral and bacterial infections. Infections like cytomegalovirus (CMV), parvovirus B19, and certain strains of E. coli are believed to initiate antiphospholipid antibody production. This occurs through molecular mimicry: the immune system creates antibodies to fight the invader, but those antibodies mistakenly cross-react with similar human proteins. Certain medications, such as anti-epileptic drugs or the combined oral contraceptive pill, are also potential non-genetic triggers for APS.
Family Screening and Monitoring
Family members of an individual with APS have an increased chance of having antiphospholipid antibodies, even if they show no symptoms. Universal screening is not typically recommended for asymptomatic relatives; instead, testing is reserved for those with suggestive symptoms or specific risk factors. Screening is most relevant for women planning pregnancy or for any relative experiencing an unexplained clotting event.
The screening process involves a blood test to check for the persistent presence of the three main antiphospholipid antibodies: lupus anticoagulant, anti-cardiolipin antibodies, and anti-beta-2-glycoprotein I antibodies. To confirm a sustained presence, a positive result must be repeated at least 12 weeks after the initial test. Relatives who test positive for aPL antibodies should be closely monitored by a healthcare professional for early signs of APS, such as recurrent headaches, unexplained skin rashes, or any indication of a blood clot.