The prevalence, onset, and clinical significance of antiphospholipid antibodies prior to diagnosis of systemic lupus erythematosus

Abstract

Objective. To determine whether antiphospholipid antibodies (aPL) occur before the diagnosis of systemic lupus erythematosus (SLE) and before initial clotting events, and whether their presence early in the disease course influences clinical outcome.Methods. Serum samples obtained from 130 lupus patients before and after SLE diagnosis were screened for IgG and IgM aPL using an anticardiolipin (aCL) enzyme-linked immunosorbent assay. Medical records of all patients were carefully reviewed for data on the time of onset of SLE features meeting clinical criteria and on disease manifestations.Results. Twenty-four patients (18.5%) were positive for IgG and/or IgM aCL prior to SLE diagnosis. Anticardiolipin antibodies appeared from 7.6 years prior to SLE diagnosis to within the same month as SLE diagnosis, with a mean onset occurring 3.0 years before SLE diagnosis. Additionally, aCL presence early in the disease process seemed to predict a more severe clinical outcome; these patients eventually met an average of 6.1 of the 11 classification criteria for SLE, compared with 4.9 criteria for other patients (P < 0.001). The early aCL-positive population also had more frequent renal disease, central nervous system disease, thrombocytopenia, and clotting events. In this population, aCL preceded initial thrombotic events by a mean of 3.1 years.Conclusion. Anticardiolipin antibodies in SLE patients tend to precede initial clotting events by several years. Furthermore, the presence of early, prediagnosis aPL seems to herald a more varied, severe clinical course with earlier onset in patients with SLE.

Ro 60 functions as a receptor for β2‐glycoprotein I on apoptotic cells

“…autoantibody; and the role of ␤ 2 GPI-Ro 60 complexes in the clearance of apoptotic cells, given that both proteins may be natural ligands for apoptotic cell engulfment (3,14). The potential role of surface-exposed ␤ 2 GPI-Ro 60 complexes in the induction of autoimmune responses to these autoantigens, both of which appear to be targeted early in human SLE (35,36), also deserves further consideration.…”

Are we at a stage to predict autoimmune rheumatic diseases?

“…In the same group of 130 SLE patients described by Arbuckle et al, McClain et al (8) highlighted the fact that moderate or high levels of aCL were present in 24 patients (18.5%) up to 7.6 years before SLE diagnosis (mean 3.1 years). Of these 24 patients, 12 (50%) had a clinical thrombotic event (venous or arterial or recurrent spontaneous abortions), with all but 1 occurring prior to SLE diagnosis.…”

Immunization with an Apoptotic Cell-Binding Protein Recapitulates the Nephritis and Sequential Autoantibody Emergence of Systemic Lupus Erythematosus

“…Our data indicate that a long-lived T cell response to a single heterologous protein (e.g., human ␤ 2 GPI) can give rise to autoimmunity in a healthy nonautoimmune host if this protein interacts with a scaffold containing multiple autoantigens (i.e., the apoptotic cell) on which epitope spread can occur. It is notable that ␤ 2 GPI represents one of the first autoantigens targeted in human SLE (1), and that the presence of aPL predicts an earlier appearance of anti-dsDNA and anti-Sm Abs, as well as a more severe clinical outcome (11). Autoantibodies can be detected in SLE patients up to 9.4 years before diagnosis, with the number of autoantibodies increasing over time (1).…”

“…Second, it was necessary to generate a strong and persistent T cell response to the inciting immunogen. To address the first issue, we selected human ␤ 2 -glycoprotein I (␤ 2 GPI), a heterologous protein that readily binds to apoptotic cells and appears to be one of the first autoantigens targeted in humans developing SLE (1,11). To minimize the effects of apoptotic cells, we immunized normal mice with soluble heterologous ␤ 2 GPI and relied on the fact that heterologous ␤ 2 GPI would interact with endogenous apoptotic cells.…”