HETEROGENEITY AND CLINICAL-SIGNIFICANCE OF GLOMERULAR-BINDING ANTIBODIES IN SYSTEMIC LUPUS-ERYTHEMATOSUS

We used an ELISA employing extracts of human glomerular basement membr ane (GEM) to detect, characterize, and evaluate the clinical significa nce of glomerular-binding IgG in patients with SLE nephritis. Most pat ients with SLE nephritis exhibited GEM-binding IgG, although many pati ents with active nonrenal SLE or symptomatic, drug-induced lupus had s imilar reactivity, albeit at lower levels. IgG binding to GEM in SLE n ephritis patients was decreased by DNase pretreatment of GEM, restored after DNase with nuclear antigens (most notably with nucleosomes), in hibited by exogenous nuclear antigens (particularly nucleosomes), but unaffected by exposure of serum to DNase/high ionic strength. The char acteristics of IgG binding to GEM largely paralleled the patients' und erlying autoimmune response, which was dominated either by antibodies to DNA/nucleosomes or to nucleosomes alone. Binding of lupus sera to n onrenal extracellular matrix (even with nucleosomes) was not equivalen t to GBM. Collagenase pretreatment of GEM variably decreased IgG bindi ng, depending on the level and type of binding. SLE nephritis patients with high levels of GEM-binding IgG exhibited more severe disease cli nically, but the same renal histopathology, as patients with lower lev els. The level of GEM-binding IgG at presentation did not predict the therapeutic response, but decreased in responders to therapy. In sum, glomerular-binding IgG in lupus nephritis binds to epitopes on chromat in, which adheres to GEM in part via collagen. These autoantibodies ap pear necessary, but not sufficient, for the development of nephritis, and correlate with clinical rather than histopathologic parameters of disease activity.