Precision-Medicine Could Improve Rheumatoid Arthritis Treatment


A better understanding of the mechanisms of arthritis is needed to develop superior treatments.

New research is continuously identifying the underlying mechanisms of inflammatory arthritis, which leads to better understanding of the disease and new treatments.

Experts involved with this research presented their findings during the Innovative Research in Inflammatory Arthritis session at the American College of Rheumatology and Association of Rheumatology Health Professionals annual meeting.

Adam Mor, MD, PhD, assistant professor of Medicine and Pathology at New York University School of Medicine, discussed how T cells play a key role in rheumatoid arthritis.

T cells from these patients do not adhere well, and his research has found that the programmed cell death protein receptor is a regulator of T cell adhesion, and affects how T cells function in patients with rheumatoid arthritis (RA).

“This is important, because feeding the cells with the ligand of the receptor could be a good treatment for RA,” Dr Mor said.

Other factors also contribute to the mechanisms behind inflammatory arthritis.

“Glycosylation of the Fc (fragment crystallizable) portion of IgG (immunoglobulin-G) affects the effector capacity of antibodies, rendering them more or less potent at triggering inflammation,” said Peter A. Nigrovic, MD, Associate Professor at Harvard Medical School in Boston and director of the Center for Adults with Pediatric Rheumatic Illness.

IgG glycans change during childhood, and may make antibodies more pro-inflammatory when it comes to arthritis.

“These studies of normal glycan variation have now enabled us to define the first in vivo modulator of human IgG Fc glycoscylation,” Dr Nigrovic said.

Genomic approaches could also be used to better understand the pathogenesis of arthritis, and lead to more targeted treatments. Harris R. Perlman, PhD, Professor of Medicine and Chief of Rheumatology at the Northwestern University Feinberg School of Medicine noted how gene expression signatures of monocytes and synovial macrophages in RA can accomplish that goal.

Non-classical monocytes are critical for the development of rheumatoid arthritis in mice. If the cells are eliminated in the animal models, the disease will not develop, according to Dr Perlman.

The monocytes infiltrate the joints and then differentiate into macrophages. Dr Perlman and his team of researchers discovered that macrophages are heterogeneous and create multiple populations. In patients with RA, macrophages that originated in the joints are overwhelmed by the monocytes that enter the joints during disease progression.

A better understanding of the differences between the macrophages could potentially improve treatment.

“The end goal is to develop transcriptional profiles of the macrophage population,” Dr Perlman said.

Initially, researchers would use a mouse model and then verify it with human data derived from ultrasound-guided synovial biopsies, which could offer genomic signatures for a response to treatment, according to the study.

It is also possible to determine if pathways, such as TNF-alpha signaling or the IL-6 signaling pathways, are activated inside the cell. This information could identify new drugs and forms of pathogenesis that was not previously known.

This precision medicine approach has already been widely used in the oncology space, and has only begun to be used in rheumatology.

“It’s a multipronged approach, and it’s extremely powerful — a couple of years ago we could never have thought this, and now we can,” Dr Perlman said. “This is paradigm shifting, it could change how we treat patients. That’s what we’re doing this for, to have that type of impact.”

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