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You are here: Home / Articles / Experts Discuss the Latest Precision Medicine Research

Experts Discuss the Latest Precision Medicine Research

February 18, 2018 • By Susan Bernstein

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Personalized immunomonitoring, or studying gene expression profiles to identify molecular pathways linked to disease activity, was used in a recent pediatric SLE study.6 Researchers looked at 486 gene transcripts in 158 pediatric lupus patients and 48 healthy controls, and found that children with elevated disease activity had specific interferon and plasmablast signatures.

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Because lupus is highly heterogeneous, “each individual patient seems to have different modules that may be important to their disease and their disease activity,” said Dr. James. Transcriptional immunomonitoring is an intriguing tool for lupus research, but “the challenge is that some parts of these modules are driven by genetics, which can lead to constant changes in the modules for subsets of patients. Concurrent infections can also change expression in some modules, so additional investigation, especially in adult patients, can help the practicing clinician know if we can stop the patient’s therapy, or if a patient needs more aggressive therapy.” Additional modules may also help identify patients at higher flare risk before they come into the office, she said.

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Current research on soluble mediators, such as complements, autoantibodies, cytokines, chemokines and shed receptors, may help complete the puzzle. In a 2017 study of African-American lupus patients, researchers found soluble mediators that suggested which patients were about to flare.7 This research could help develop an algorithm or “soluble mediator score” to help select patients for future clinical trials, or point to which patients need therapy modifications, she said.

Precision Medicine in JIA

Rheumatology currently views pediatric and adult arthritis as two separate disease families, but they should be viewed as a continuum, said Peter A. Nigrovic, MD, director at the Center for Adults with Pediatric Rheumatic Illness at Brigham and Women’s Hospital, and associate professor of medicine at Harvard Medical School, both in Boston, Mass. Further, using GWAS data to identify similar forms of arthritis across age groups may lead to better understanding of disease mechanisms, he said.

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“Adult and pediatric arthritis have historically been described using totally distinct nomenclatures, and this has had consequences,” said Dr. Nigrovic. “Treatment algorithms begin with naming the disease for which they are intended to be used. Insurers approve medications for some diseases and not others. Researchers include only patients with a particular disease in their studies. Any attempt at precision medicine therefore requires that we get the nomenclature right. But it’s not easy to decide what goes with what.”

Disease classification should anchor on the “primacy of pathogenesis,” encompassing genetics and biological features as well as clinical phenotype, he said. As researchers dig more deeply into patient subgroups, both similarities and differences emerge. “Seropositive and seronegative RA are distinguished not only by the presence of certain autoantibodies, but also by the presence of immune complexes and complement fixation in joints, by the abundance of specific T cells in synovial tissues, and by environmental and genetic risk factors. Spondyloarthritis describes another family, with a distinct gender ratio and pattern of affected joints, the prevalence of enthesitis, and the prominent genetic association with HLA-B27.”

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Filed Under: Meeting Reports, Rheumatoid Arthritis, SLE (Lupus) Tagged With: ACR/ARHP Annual Meeting, Arthritis, big data, Genetic research, genomics, Lupus, Precision Medicine, Rheumatoid arthritisIssue: February 2018

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