SNOWMASS, COLO. — Promising new biomarkers of complement turnover may provide a rapid measure of lupus activity over a defined time period.
This would be enormously helpful to physicians in monitoring disease activity accurately, predicting flares, and adjusting treatment accordingly. Measurement of C3 and C4, long the standard means of assessing the disease state, leave much to be desired, Dr. John P. Atkinson observed at a symposium sponsored by the American College of Rheumatology.
The novel biomarkers are the result of pioneering work by Dr. Joseph M. Ahearn and his colleagues at the University of Pittsburgh. They took advantage of the fact that in times of increased systemic lupus erythematosus (SLE) activity patients experience accelerated complement turnover.
The investigators identified fragments of the cleaved complement and showed that these fragments are deposited on the surface of many types of cells, including RBCs, platelets, and polymorphonuclear neutrophils. The amount of deposited complement-activation product C4d correlates with disease activity, while complement receptor type 1 deposition varies inversely with SLE activity, explained Dr. Atkinson, the Samuel B. Grant Professor of Clinical Medicine at Washington University at St. Louis.
The half-lives of RBCs, platelets, and polymorphonuclear neutrophils are about 60 days, 7 days, and 3 days, respectively. Depending upon which cell type is assessed for fragment deposits, physicians can obtain a picture of SLE activity over the course of a very different period of time.
Also, there is some preliminary evidence to suggest platelet C4d deposition might predict future vascular events in SLE patients with antiphospholipid antibodies.
Clinical trials are underway to assess the clinical utility of the new biomarkers.
The rheumatologist disclosed he has no financial conflict of interest with regard to the biomarkers but serves as a consultant to or is on the scientific advisory boards of several pharmaceutical companies.