It is not clear how generalizable these results are, based on the small number of patients in this study. Dr. Orange et al. are currently working on another analysis with a larger patient set, which will examine whether background therapy affects this pattern of immune activation.
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If the results are generalizable, it might be possible to intervene prior to flare onset, if patients were regularly monitoring their blood for detectable changes. This might not be practical in the end, but the insights into pathophysiology and immune responses could have long-term impacts on therapy development. Dr. Orange also speculates, “It does also suggest that if these cell types are activated just before a flare—they are sort of a smoking gun. Maybe if you targeted these PRIME cells, maybe we could prevent flares.”
The broad use of such an approach—using longitudinal genomics to identify key precursors of disease flares—may be applicable for multiple types of rheumatic disease. Dr. Orange points out that such an approach requires an outcome measure, similar to the RAPID3, which can reliably measure disease activity from home. “I think this approach could be used for a lot of chronic inflammatory diseases that wax and wane over time,” she adds.
One of the authors of the accompanying editorial is the ACR’s immediate past president, Ellen M. Gravallese, MD, chief of the Division of Rheumatology, Inflammation and Immunity at Brigham and Women’s Hospital and the Theodore Bevier Bayles Professor of Medicine at Harvard Medical School, Boston.2 She concludes, “This study is important from both the technical standpoint, utilizing serial blood samples from patients in their homes to perform detailed molecular and cellular analyses, and from the standpoint of the information gained about the mechanisms of rheumatoid arthritis flares.”
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.
- Orange DE, Yao V, Sawicka K, et al. RNA identification of PRIME cells predicting rheumatoid arthritis flares. N Engl J Med. 2020 Jul 16;383(3):218¬–228.
- Gravallese EM, Robinson WH. PRIME time in rheumatoid arthritis. N Engl J Med. 2020 Jul 16;383(3):278–279.
- Zhang F, Wei K, Slowikowski K, et al. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nat Immunol. 2019 Jul;20(7):928–942.
- Mizoguchi F, Slowikowski K, Wei K, et al. Functionally distinct disease-associated fibroblast subsets in rheumatoid arthritis. Nat Commun. 2018 Feb 23;9(1):789.
- Croft AP, Campos J, Jansen K, et al. Distinct fibroblast subsets drive inflammation and damage in arthritis. Nature. 2019 Jun;570(7760):246–251.