At UC, researchers have been defining high-risk patients as those with anticyclic citrullinated peptide 2 (antiCCP2) antibodies, or two or more rheumatoid factors, or both, which has been shown to be 95% specific for future RA. But, predicting who will get RA is one thing, and understanding how to prevent it is another, Dr. Holers said.
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Explore This IssueJanuary 2013
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“We not only want to be able to predict clinical onset, we want to identify the site and the mechanisms of the onset of the disease,” he added.
For the last eight years, the Studies of the Etiologies of Rheumatoid Arthritis (SERA) project at UC has been trying to get at some of these specifics by looking at, among other things, the levels of ACPA in antiCCP2-positive subjects, and at chemokine and cytokine levels.
A possible candidate for further exploration, Dr. Holers said, is the use of a “cytokine score.” Researchers determine—for a variety of cytokines—the odds ratio that the cytokine will be linked to a high-risk RA autoimmunity status. The total of those odds ratios is the cytokine score.4
Team Approach to Research
A team approach across disease specialties will make prevention therapies more likely, Dr. Holers said. “Autoimmune diseases are really prevalent in the population and none of us, including those with type 1 diabetes, can view their diseases individually,” he continued. “They all have a very similar kind of evolution. They all have biomarkers, mostly antibodies in the preclinical phase.”
Michael Brenner, MD, professor of medicine at Harvard University in Boston, and chief of rheumatology, immunology and allergy at Brigham and Women’s Hospital in Boston, said that “nature is pointing us to something that may be useful” in developing antigen-specific treatments to replace the blunter tools now at rheumatologists’ disposal.
Studies are beginning to show antigen-specific behavior by T cells, Dr. Brenner said.5,6 “The possibility to expand or direct T-regs in vivo to relevant self antigens is what evolution has come up with to control T-cell autoreactivity,” he said. “And I think it may have an important lesson to at least point us in the direction in which we may be able to apply the self-antigen adaptive immunity that we’ve been seeking since the T-cell receptor was discovered.”
Another direction toward a possible cure might be focusing on the role of certain cadherins—adhesion molecules that effectively glue our cells together—in damage to the joints. “We focus so much on inflammation in rheumatoid arthritis, but we can also benefit from focusing on protecting the joint directly,” he added.