A 52-Year-Old Lupus Paper Remains Important Today

Dr. Pisetsky

Dr. Pisetsky says a variety of assays then existed that could be used to measure anti-DNA. “We’re going back a long time ago, so the techniques were much more crude than those available today. Nevertheless, it was possible to come up with an effective quantitative assay.”

Dr. Schur performed all the assays himself. Using the Ouchterlony immunodiffusion technique, Dr. Schur identified serum antibodies to various forms of DNA (as well as free DNA) and antibodies to some other nuclear proteins. He also assessed the presence of antibodies to DNA that fixed complement. Additionally, Dr. Schur measured the total serum hemolytic complement, using a bioassay designed to assess the hemolytic potential of the complement system.

Dr. Schur explains that most people now just measure two components of the comple­ment system, C3 and C4, but good assays for those complement proteins were not available at the time. Instead, he used a test known as CH50. While at Walter Reed, he had learned how to do this test, which assesses the entire complement system. Dr. Schur explains that this technique was more sensitive than another one then commonly used to assess the complement system, the Kabat technique.

Dr. Schur and Dr. Sandson found that most, though not all, of the patients with high titers of complement-fixing antibodies to DNA had active renal disease. Not all of the patients who had very low complement levels had active renal disease. But all of the patients who had both high amounts of complement-fixing antibodies to DNA and low serum complement levels had active renal disease. Only 13% of patients with active renal disease had no anti-DNA antibodies and normal complement.¹

Dr. Schur notes that it recently had been shown that lupus nephritis patients typically had high anti-DNA and low complement levels.⁶ That pattern was confirmed in this paper, but a new predictive element was revealed as well.

In the paper, Dr. Schur and Dr. Sandson provided a brief case study of a 17-year-old girl with lupus nephritis, J.B. In the article, they tracked her clinical course and laboratory findings and displayed them graphically.

“A pattern began to evolve—it’s shown in Figure 1 as sort of a typical patient,” says Dr. Schur. “As levels of antibody to DNA increased and complement levels diminished, it often preceded a clinical flare. And if you treated them—which at the time was steroids and immunosuppressives—the anti-DNA levels went down and the complement levels went up.”