Autoimmune Protein S Deficiency

Posted by Elaine Moore Jun 4, 2007

Protein S is a plasma protein involved in the regulation of another protein known as protein C. Protein S acts as a cofactor necessary for the activation of protein C, and the activation of protein C is necessary for a cascade of steps leading to the inactivation of certain clotting factors. Without adequate protein S, this normal anticoagulant pathway that keeps circulating blood from clotting wouldn’t work properly. Consequently, circulating blood would form clots or emboli that could block normal blood flow and fail to nourish vital organs.

Usually, protein S deficiency is caused by a congenital mutation. However, transient conditions of acquired or autoimmune protein S deficiency may occur, especially in children, after infection with chicken pox or other organisms. Permanent conditions of acquired (autoimmune) protein S deficiency, which is considered one of the lupus anticoagulants, has also been reported to occur in patients with nephropathy (kidney disease) occurring as a complication of systemic lupus erythematosus, in patients with Graves’ disease, and in patients with HIV infection. Whether congenital or acquired, protein S deficiency is associated with an increased risk of venous and arterial blood clots, miscarriage, and stroke.

Autoimmune Protein S Deficiency

Transient conditions of protein S deficiency resulting in post-infectious idiopathic purpura fulminans or thromboembolisms (blood clots) have been found to occur about 7 to days after the onset of a precipitating infection. The direct cause of the protein S deficiency in these cases is IgG and IgM antibodies to protein S. These antibodies, which can spontaneously develop in people with other autoimmune conditons, destroy protein S resulting in undetectable levels.

Symptoms include a rapidly progressive purpura or bruising leading to extensive areas of skin necrosis as blood flow to organs is impaired. Impaired blood flow to the limbs or digits can cause a peripheral gangrene, blood clots to the lungs or heart or to the kidneys.

Antiphospholipid Syndrome

Antiphospholipid antibodies may also occur as a sequelae to infection or a feature of other autoimmune disorders. Antiphospholipid and anticardiolipin antibodies can contribute to deficiencies of protein S as well as the development of antiphospholipid syndrome. Although antibodies to protein S typically decline during the post-infection period, phospholipids and cardiolipin antibodies can persist indefinitely.

Diagnosis

In autoimmune protein S deficiency, levels of protein S antigen and C4b-binding protein are low, and levels of protein S antibody, erythrocyte sedimentation rate, C-reactive protein and lactic dehydrogenase (LDH) levels are elevated. Protein C levels remain normal although activated C protein levels are decreased, which suggests that an inhibitor of protein C is present. Additional findings in patients with transient post-infectious conditions of autoimmune protein S deficiency may include a slightly elevated titer of anti-smooth muscle antibodies and a modest elevation of anti-cardiolipin antibodies.

Treatment

Treatment consists of transfusions of fresh frozen plasma and tissue-type plasminogen activator to prevent blood clotting. In most cases of post-infectious protein S deficiency, the levels of protein S autoantibodies decline within 3 to 6 months at which type normal coagulation processes are restored.

Resource:

Armando D’Angelo, Patrizia Della Valle, Luciana Crippa, et al, Autoimmune Protein S Deficiency in a Boy with Severe Thromboembolic Disease, The New England Journal of Medicine, June 17, 1993; 328(24): 1753-1757.