Immunologic markers for differentiation of autoimmune responses

Several approaches have been directed at identifying accurate parameters for the measurement of disease activity in autoimmune disorders, both in humans and in experimental animal models. A great deal of previous effort has focused on determining what constitutes antigenic epitopes on various autologous proteins or tissue components, which then can generate an immune response in the host. Much of this work has been clouded by the fact that normal subjects (both animal and human) seem to mount an immune response to myriad autologous proteins, characterized by the formation of antibodies known as natural autoantibodies. During the course of certain autoimmune diseases such as systemic lupus erythematosus (SLE) or Wegener's granulomatosis (WG), patients produce what appear to be autoantibodies reacting with autologous components such as DNA and Sm antigen (SLE) or proteinase-3 (WG). Low levels of these same autoantibodies are present in IgG derived from normal subjects. Recently, we have found that IgG anti-F(ab')2 from normal subjects, affinity-purified from immunoabsorbent columns of human F(ab_)2 Sepharose, exhibits not only anti-F(ab')2 but also anti-dsDNA and anti-Sm activity. These antibodies constitute an average of 0.02% of normal serum IgG. Similar findings have also been observed in SLE patients with active disease. Our findings suggest that perturbation of the idiotypic network may represent an important fundamental aspect of many autoimmune disorders.