These are a complex group of autoantibodies associated with thrombosis (arterial and venous) in primary anti-phospholipid syndrome and secondary anti-phospholipid syndrome associated with connective tissue diseases, particularly SLE, where anti-cardiolipin antibodies are frequently, but not always, the cause of lupus anticoagulant activity. The antibodies are found more commonly in patients who do not have lupus and are associated, somewhat paradoxically, with unexplained venous and arterial thrombosis, myocardial infarction, neurological symptoms, strokes in young patients and with recurrent abortion. Although anti-cardiolipin antibodies are the most commonly measured, it has been recognised that they are only one group of several specificities of anti-phospholipid autoantibodies found in these patients. Their detection has led to the definition of a new disease entity, the primary anti-phospholipid syndrome (APS). Anti-phospholipd syndrome can encompass a wider range of symptoms than clear disorders or coagulation.
Anti-cardiolipin autoantibodies can be any combination of IgG, IgM and IgA classes. IgG antibodies are the most prevalent class of autoantibody and the class with the greatest clinical correlation. Samples found to high levels of IgG anti-cardiolipin are the most likely to display overt clinical symptoms. However IgM (and possibly IgA) autoantibodies can be found either alone or combination with the IgG. IgG and IgM anticardiolipin antibodies are measured routinely in this laboratory since there is no clear concensus on the importance or otherwise of IgA anti-cardiolipin. Levels of anticardiolipin antibody or the class of antibody class do have clear correlation with the extent or severity of thrombosis.
Anti-phospholipid antibodies have a particular value during pregnancy where they are associated with (recurrent) spontaneous abortion and perinatal thrombosis. In most cases these antibodies are detected in women with no prior evidence of connective tissue disease though they may be an indicator of subsequent connective tissue disease.
Anti-phospholipid syndrome is thought to be manifested by a wide range of symptoms. Anti-phospholipid antibodies are also found in a number of infectious diseases and also in some patients with cancer. Anti-cardiolipin antibodies may also be recognised as the anti-M1 mitochondrial antibodies and are certainly responsible for the false positive VDRL (syphilis) test occasionally seen in lupus patients. Anti-cardiolipin antibodies associated with infection such as syphilis, malaria, parasitic diseases or infectious mononucleosis tend to have different specificity to those associated with anti-phospholipid syndrome. Those associated with infection often disappear if sera are retested after 8-12 weeks.
Anticardiolipin antibodies associated with anti-phospholipid syndrome are thought to recognise a serum protein α2-glycoprotein 1 which associates with phospholipid. The assay used in this laboratory contains α2-glycoprotein. Infection related anticardiolipin antibodies are thought not to involve α2-glycoprotein 1.
The complexity of this group of autoantibodies is well documented. Some are also detected by the lupus anticoagulant assay whilst others are not. Less commonly, patients with lupus anticoagulant do not have detectable anti-cardiolipin antibodies. Anti-cardiolipin can be positive in patients without major thrombotic problems but can define patients with antiphospholipid syndrome who have no lupus anticoagulant, including patients with the so called catastrophic antiphospholipid syndrome. Anti-cardiolipin antibodies, the lupus anticoagulant test and the VDRL detect overlapping but not identical populations of antibodies. Therefore both anti-cardiolipin antibodies and lupus anticoagulant activity should be measured.
Anti-cardiolipin antibodies are by definition a major criterion for a diagnosis of APS. They are found in around 30-40% of patients with SLE. In both patients with primary and SLE associated APS positive results correlate with a predisposition for arterial or venous thrombosis, foetal loss, and thrombocytopoenia. However, levels of anti-cardiolipin antibodies do not correlate well with disease activity or with specific features of SLE such as arthritis or renal involvement.
In spite of the complexity, variability and indeed, controversy concerning these antibodies, the presence of persistent anticardiolipin antibodies serves as a marker for the risk of a thromboembolytic events. Those SLE patients exhibiting high levels of these autoantibodies are 4 times more likely to have such an event than those not expressing the autoantibodies. They are also found in up to 20% of young stroke patients (particularly males). Anticardiolipin antibpodies, in contract to lupusanticoagulant, can be measured in patients with current or recent anti-coagulant therapy.