Serum anti-beta2-glycoprotein-I and anticardiolipin antibodies during thrombosis in systemic lupus erythematosus patients.

PURPOSE: Antibodies to beta2-glycoprotein-I are more strongly associated with clinical antiphospholipid syndrome than are anticardiolipin antibodies. We previously found a decrease in anticardiolipin antibodies at the time of thrombosis in 6 patients with systemic lupus erythematosus (SLE). We therefore sought to determine the prevalence and levels of antibodies to beta2-glycoprotein-I and to cardiolipin before, during, and after thrombosis in patients with SLE, and to compare them with patients who did not have thrombosis. METHODS: We studied 24 patients with SLE who had at least one episode of thrombosis and 102 patients with SLE without thrombosis. Serum anticardiolipin antibodies were measured by conventional enzyme-linked immunosorbent assay (ELISA) using newborn calf serum as the blocking agent. Serum anti-beta2-glycoprotein-I antibodies were measured by ELISA on nonirradiated plates, using purified human beta2-glycoprotein-I without phospholipid. RESULTS: All patients with thrombosis had anti-beta2-glycoprotein-I antibodies, compared with only 17% of controls (P <0.0001). We observed a significant decrease in serum anti-beta2-glycoprotein-I levels at the time of thrombosis, as compared with previous and subsequent samples. The prevalence and levels of IgG and IgM anticardiolipin antibodies were similar in patients with and without thrombosis. A decrease in IgG or IgM anticardiolipin titers occurred during thrombosis in 6 patients. Anticoagulant, corticosteroid, and immunosuppressive treatments did not appear to affect anti-beta2-glycoprotein-I levels at the time of thrombosis. CONCLUSION: Anti-beta2-glycoprotein-I antibodies are strongly associated with thrombosis in patients with SLE. The decrease of anti-beta2-glycoprotein-I levels at the time of thrombosis may indicate a pathogenic role. This antibody may also be a marker of predisposition for thrombosis in these patients.

Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus. A prospective analysis of 500 consecutive patients.

Five hundred consecutive patients with systemic lupus erythematosus (SLE) were entered into a prospective study of anticardiolipin antibodies (ACLA) in their 3 major immunoglobulin isotypes and followed thereafter with repeated testing for a mean period of nearly 8 months. Manifestations of SLE that were strongly associated with ACLA included venous thrombosis (particularly when recurrent), thrombocytopenia, hemolytic anemia, recurrent fetal loss, and leg ulcers. Other manifestations found to be associated with ACLA were arterial occlusions, transverse myelitis, and pulmonary hypertension. Conversely, we found no relationship between ACLA and migraine, convulsions, transient ischemic attacks, psychoses, or avascular necrosis of bone. No relationship was found between the presence of ACLA and that of anti-DNA antibodies studied in the same serum sample. Association with ACLA grew stronger and titers became higher in patients with several of the associated manifestations. Statistical analyses revealed the existence of a syndrome, the antiphospholipid syndrome, comprising 2 or more manifestations in conjunction with ACLA titers 5 standard deviations above the mean of normal control subjects, particularly if ACLA had been positive on at least 2 occasions. We propose that such criteria could be applied to the definition of the antiphospholipid syndrome. The presence and the titers of these antibodies related to disease activity and titer decreased by treatment, particularly when they were of the IgM isotype. Patients in whom a thrombotic episode occurred during the course of the study were observed to have a coincident decrease in ACLA titers, a finding that might indicate consumption of the antibody during the event. Treatment and the resulting inactivation of disease appear to have independent effects on ACLA titers. Physicians should therefore be cautious in prescribing high doses of corticosteroids or immunosuppressants to patients with SLE solely because they have high titers of ACLA.

Hemocytopenia in systemic lupus erythematosus. Relationship to antiphospholipid antibodies.

We studied 500 consecutive patients with systemic lupus erythematosus (SLE) for antibodies to phospholipids (APLA) by an ELISA method using cardiolipin as antigen and antiimmunoglobulins G, M and A to determine their isotype. Once entered into this prospective study the patients were followed for up to 16 months (mean 7.7 +/- 4.72 SD) with periodic determinations of APLA. Of the 500 patients with SLE, 88 had had thrombocytopenia, 25 had had hemolytic anemia, 25 had had both, and 362 had no history of these hemocytopenias. If we considered the odds ratio of these 362 patients for having high titer APLA as 1, patients with a history of thrombocytopenia, hemolytic anemia or both had significantly higher odds ratios of having APLA than did those without hemocytopenia. Patients with thrombocytopenia had significantly higher levels of IgG APLA, those with hemolytic anemia had significantly higher titers of IgM APLA and patients with both had significantly higher titers of both of these APLA isotypes, than did patients without hemocytopenias. A correlation between positive direct Coombs' tests and IgM APLA was also found. We conclude that APLA is associated with these hemocytopenias in SLE. This might be due to their interaction with negatively charged phospholipids in the cell walls of the respective cells.