Cross-reactivity between anti-cardiolipin, anti-high-density lipoprotein and anti-apolipoprotein A-I IgG antibodies in patients with systemic lupus erythematosus and primary antiphospholipid syndrome

Abstract

Objectives. Atherosclerosis is an important complication of patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS). One suggested mechanism may be the action of autoantibodies directed against plasma lipoproteins. We studied the presence and patterns of cross‐reactivity between antibodies directed against cardiolipin, high‐density lipoprotein (HDL) and apolipoprotein A‐I (Apo A‐I) in patients with SLE and APS. Methods. Sera from 50 patients (25 SLE and 25 APS) and 10 healthy controls together with three human immunoglobulin G anti‐cardiolipin (CL) monoclonal antibodies (IS4, CL1 and CL24) were assessed for the presence of autoantibodies binding cardiolipin, HDL and Apo A‐I. Classical inhibition assays were performed to study interference by HDL and Apo A‐I in the binding of the human monoclonal antibody to CL. To determine the cross‐reactivity patterns between these autoantibodies, sera from 12 patients were incubated on ELISA plates coated with the three different molecules and the captured antibodies were then tested for their activity towards each of the other antigens. Results. All three monoclonals bound to CL. IS4 and CL1 also bound to HDL but only IS4 bound to Apo A‐I. Anti‐cardiolipin titres were higher in patients with APS than SLE and in healthy controls (PPPPr=0.563, PConclusions. Patients with SLE and APS have antibodies directed against HDL and Apo A‐I. A high percentage of these antibodies cross‐react with CL, suggesting the presence of different groups of antibodies with different targets. The study of the interaction between the immune response and the lipoprotein components and the correct characterization of the reactivity patterns of autoantibodies may be of relevance in the study of atherosclerosis in patients with SLE and APS.