Antiphospholipid syndrome (APS) is an autoantibody-mediated acquired thrombophilia characterized by recurrent arterial or venous thrombosis and/or pregnancy morbidity. The major autoantibodies detected in the patient’s sera are directed against phospholipid (PL)-binding plasma proteins, mainly against a 43-kDa plasma apolipoprotein known as β2 glycoprotein I (β2GPI) and prothrombin. The plasma concentration of β2GPI is 50–200 μg/mL. β2GPI consists of 326 amino acids arranged in five domains (I through V). Domain V forms a positively charged patch, suitable to interact with negatively charged PL. In plasma, β2GPI has a circular conformation with domain V binding to and concealing the B cell epitopes lying on domain I. Another group of antibodies termed lupus anticoagulant (LA) elongate clotting times in vitro; this elongation is not corrected by adding normal plasma to the detection system (Table 379-1). Patients with APS often possess antibodies recognizing Treponema pallidum PL/cholesterol complexes, which are detected as biologic false-positive serologic tests for syphilis (BFP-STS) and Venereal Disease Research Laboratory (VDRL) tests. APS may occur alone (primary) or in association with any other autoimmune disease (secondary). Catastrophic APS (CAPS) is defined as a rapidly progressive thromboembolic disease involving simultaneously three or more organs, organ systems, or tissues leading to corresponding functional defects.
Anti-PL (aPL)-binding plasma protein antibodies occur in 1–5% of the general population. Their prevalence increases with age; however, it is questionable whether they induce thrombotic events in elderly individuals. One-third of patients with systemic lupus erythematosus (SLE) (Chap. 378) possess these antibodies, whereas their prevalence in other autoimmune connective tissue disorders, such as systemic sclerosis (scleroderma), Sjögren’s syndrome, dermatomyositis, rheumatoid arthritis, and early undifferentiated connective tissue disease, ranges from 6 to 15%. One-third of aPL-positive individuals experience thrombotic events or pregnancy morbidity.
TABLE 379-1Classification and Nomenclature of Antiphospholipid Antibodies |Favorite Table|Download (.pdf) TABLE 379-1 Classification and Nomenclature of Antiphospholipid Antibodies
|Name ||Assay for their Detection ||Comments |
|Antibodies against cardiolipin (aCL) ||Enzyme-linked immunosorbent assay (ELISA) using as antigen cardiolipin (CL), a negatively charged phospholipid ||aCL from patients with APS recognize β2GPI existing in the human serum as well as in bovine serum, which is used to block the nonspecific bindings sites on the ELISA plate. CL simply stabilizes β2GPI at high concentration on the polystyrene surface. |
|Antibodies against β2GPI (anti-β2GPI) ||ELISA using as antigen affinity purified or recombinant β2GPI in the absence of PL ||Antibodies recognize β2GPI bound in the absence of CL to an oxidized polystyrene surface, where oxygen atoms in the moieties C-O or C=O were introduced by γ-irradiation. |
|Lupus anticoagulant (LA) || |
Activated partial thromboplastin time (aPTT)
Kaolin clotting time (KCT)
Dilute Russel viper venom test (DRVVT)
|Antibodies recognize β2GPI or prothrombin (PT) and elongate aPTT, implying that they interfere with the generation of thrombin by prothrombin. Prolongation of the clotting times is an in vitro phenomenon, and LA induces thromboses in vivo. |