[Clinical significance of the detection of anti-nuclear antibody-associated idiotypes].

Idiotypes (Id) are unique structures in hypervariable regions of immunoglobulin and can be identified by the corresponding anti-Id antibodies. We developed a new way to recognize pathogenic autoantibodies through idiotypes. O-81 and NE-1 are human monoclonal anti-DNA antibodies expressing O-81 Id and NE-1 Id, which are recognized by mouse monoclonal anti-Id antibodies, DIE2 and IF5 respectively. Using these antibodies, we have analyzed the clonotypes of anti-DNA antibodies expressing specific idiotypes in serum or tissue. Anti-DNA antibodies expressing specific idiotypes, termed O-81 and NE-1 Id were detected only in the immune complexes of patients with active lupus nephritis. Anti-DNA clonotypes including O-81 and NE-1 idiotypes, were also found in the eluates of the renal glomeruli of lupus patients. The incidence of O-81 Id in circulating immune complexes (CIC) in lupus patients was closely associated with diffuse proliferative lupus nephritis, whereas most cases with negative results for O-81 Id-CIC showed minimal mesangial alteration or membranous lupus nephritis. O-81 Id of human anti-DNA antibodies was also specifically detected on the immune deposits of renal glomeruli in 46% of the patients with lupus nephritis when determined by an immunofluorescence assay. We finally indicated a simple method for the detection of autoantibody-associated Id by using flow cytometry.