Are the clonotypes of serum IgG anti-DNA antibodies associated with lupus nephritis in humans?

We analyzed isoelectrofocusing (IEF) patterns of anti-DNA antibodies originated from sera and the renal eluates of patients with systemic lupus erythematosus (SLE). The spectrotypic patterns of serum anti-DNA-antibodies were heterogenous and bands with single-stranded (ss) and double-stranded (ds) DNA were detected in the PI 5.5-6.5 and PI 8-9.5 regions when SLE sera were tested, whereas healthy subjects failed to form bands even at different saline concentrations. The renal eluates from normal subjects never bound to DNA whereas those from SLE glomeruli showed relatively restricted IEF patterns which were detected mainly in PI 6.0 and PI 8.5, showing that some anti-DNA antibodies may be nephritogenic. However, the spectrotypic patterns of serum anti-DNA antibodies in patients with active lupus nephritis were similar with those in patients lacking renal lesions. The reasons why IEF analysis failed to indentify specific clonotypes of nephritogenic anti-DNA antibodies are discussed in association with pathogenesis of lupus nephritis. This study also suggests that the use of a high concentration of 6M urea in an IEF analysis may be able to expose antigen-binding sites of the circulating immune complex (IC)-derived antibodies.