Polyspecific monoclonal lupus autoantibodies reactive with both polynucleotides and phospholipids.

TLDR

Systemic lupus erythematosus is associated with spontaneous production of anti‑DNA autoantibodies in MRL/1 mice. The study examined whether these anti‑DNA monoclonal antibodies also react with phospholipids due to shared phosphodiester backbones. Hybridomas producing anti‑DNA autoantibodies were generated from spleen cells of unimmunized MRL/1 mice. The monoclonal antibodies inhibited DNA binding and anti‑idiotypic interactions by cardiolipin, phosphatidic acid, and phosphatidylglycerol, and one antibody prolonged aPTT like a lupus anticoagulant, indicating that polyspecific reactivity to phosphodiester‑containing epitopes may underlie diverse SLE serological abnormalities.

Abstract

Hybridomas the produce anti-DNA autoantibodies were prepared from spleen cells of unimmunized MRL/1 mice, a strain that spontaneously develops severe systemic lupus erythematous (SLE). Reactivities of these monoclonal antibodies with a wide range of polynucleotides prompted tests of their reactions with phospholipids which, like polynucleotides, contain diester-linked phosphate groups in their backbones. In competitive radioimmunoassays, cardiolipin, phosphatidic acid, and phosphatidyl glycerol blocked the binding of these hybridoma antibodies to denatured DNA. These phospholipids also specifically inhibited the reaction between a hybridoma antibody and a site-specific anti-idiotypic antibody. The antinuclear reaction of one of these antibodies was specifically inhibited by cardiolipin. This same antibody prolonged the activated partial thromboplastin time in a manner characteristic of a lupus anticoagulant, presumably by binding to phospholipid in the test system. The polyspecific reactivity of a single molecular species of lupus autoantibody suggests that some of the diverse serological abnormalities of SLE may be a result of the binding of certain autoantibodies to a phosphodiester-containing epitope that is present in diverse biological molecules.