Dr. Holers also sees the question of antibody development as a key question moving forward. “Is there epitope spreading such that there is cross-reactivity between citrullinated target proteins/antigens and then the PADs themselves?” he asks. Through this process, anti-PAD4 antibodies may develop as T and B cells develop immune responses to new epitopes through their association with the initial primary disease epitopes.2
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Dr. Holers notes it would also be interesting to explore if people with PAD autoantibodies might more favorably respond to a group of drugs currently under development, PAD inhibitor drugs.
Currently, PAD antibody tests are not available for clinical use, although industry is working on developing tests that might eventually become commercially available. Potentially, these might have value as prognostic assays. “Say you have PAD4 autoantibodies and also PAD3 cross-reactivity; that would help to stratify your risk of severe disease. Throwing in PAD2 antibody testing might give you a different piece of information,” Dr. Darrah speculates.
Although the research is promising, more work needs to be done to demonstrate clinical utility.
Ruth Jessen Hickman, MD, is a graduate of the Indiana University School of Medicine. She is a freelance medical and science writer living in Bloomington, Ind.
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