New Surrogate Markers for Autoimmune Disease Activity Editorial

A key issue in understanding the etiology of autoimmunity is the identification of pathogenic cells that cause or contribute to disease activity. Recent breakthroughs in several areas of immunobiology have spawned a new generation of surrogate markers for inflammation that may lead to the identification of pathogenic cells for autoimmune disease. Further, these mark-ers have the potential to lead to novel and more effective ways to predict and monitor disease activity and responses to ther-apy. The breakthroughs that have occurred include: the under-standing of the role of chemokines and adhesion molecules that are necessary for leukocyte extravasation into sites of in-flammation; development of intracellular cytokine assays for activated cytokine-producing cells; and the ability to assay for antigen-specific T cells using peptide-loaded, fluorochrome-conjugated MHC tetramers (Table I). Generally, pathogenic cells for autoimmune disease have been believed to have an activated phenotype manifested by high levels of MHC molecules, cytokine receptors (e.g., CD25, IL-2 receptor a), adhesion molecules (e.g., CD44), and cyto-plasmic cytokines. Many investigators have shown that the levels of cytokines and soluble adhesion molecules can be el-evated in serum, tissue, or bodily fluids during active autoim-mune disease, and these assays are being investigated for their utility in the diagnosis or monitoring of autoimmune diseases. Activated T cell subsets can now be identified and monitored by intracellular staining of cytokines using anticytokine mAbs (1). In rheumatoid arthritis, pathogenic T cells may be oligo-clonal due to DR4 alleles selecting a potentially autoreactive T cell population (2). The advent of PCR-based analyses of th