Platelet C4d Is Highly Specific for Systemic Lupus Erythematosus

What problem was studied?
Blood clots are a serious potential complication of systemic lupus erythematosus (SLE), putting people with the disease risk of heart attack, stroke and -- when clots occur in the placenta during pregnancy -- miscarriage.

In previous studies, a complement-activation product called C4d has been observed on the erythrocytes (red blood cells) of people with lupus. A complement-activation product is a small piece (C4d) of a larger protein (C4) that gets clipped off during inflammation as occurs in lupus. This study examined whether C4d also deposits on platelets in blood plasma and might be a marker for lupus and have a role in the development of blood clots and pregnancy loss in women with the disease.

What was done in the study?
Researchers supported in part by the Foundation, conducted a cross-sectional study of 105 patients with lupus, 115 patients with other forms of arthritis or autoimmune or blood diseases (including rheumatoid arthritis, scleroderma, hepatitis C, sickle cell anemia, psoriatic arthritis) and 100 healthy people.  All participants had clinical histories, physical examinations and routine laboratory tests, including tests to measure inflammation and antiphospholipid antibodies (aPL, antibodies against phospholipids -- a group of substances in cell membranes – that can occur in people with lupus and are associated with a greater risk of blood clots and pregnancy loss).

Using sophisticated laboratory tests, the researchers examined blood samples for levels of C4d on platelets (P-C4d) and then performed analyses to determine factors associated with the finding of P-C4d.

What were the study results?
This study was the first to demonstrate that C4d is deposited on human platelets and this deposition is highly specific for SLE and correlates with disease manifestations. The tests showed high levels of P-C4d in 18 percent of the patients with lupus, two patients with other diseases (one with rheumatoid arthritis, one with scleroderma) and none of the healthy control group. In people with lupus, P-C4d was significantly associated with a positive test result for lupus anticoagulant and anticardiolipin antibodies, which are associated with a higher risk of abnormal blood clotting.

Based on their findings, the researchers say it is reasonable to speculate that deposition on platelet surfaces may influence platelet aggregation (their propensity to stick to one another to form clots) or interactions with the cells that line the blood vessels (creating possible targets where blood clots might form).

What’s the relevance to people with lupus?
Based on evidence from previous studies of the crucial role of complement activation in aPL-induced fetal loss, the researchers believe that platelet C4d may serve to identify the subset of patients with the antibodies that are at high risk of a blood clot. It may also be used to identify patients without antiphospholipid antibodies who are at risk of clotting and to possibly predict other outcomes in patients with lupus. P-C4d may also provide clues to mechanisms of clotting and other blood vessel complications in people with lupus; however, further studies are needed to address the role of P-C4d as a predictor of future vascular events.

Source: Arthritis & Rheumatism, Vo. 54, No. 2