Investigators Discover Unique Immune Cells in Patients with Checkpoint Inhibitor-Induced Arthritis

Since doctors began treating cancer patients with immunotherapy drugs called checkpoint inhibitors nearly a decade ago, they have observed that a subset of these patients experience a side effect that clinically looks like inflammatory arthritis. These drugs, which take the natural brake off immune cells called T cells and allow them to attack cancer, can result in T cells also attacking healthy tissues, including the joints.

Now a study from investigators at Hospital for Special Surgery (HSS) and Brigham and Women’s Hospital in Boston has found that the synovial fluid and blood of people experiencing checkpoint inhibitor-induced arthritis is populated by a type of T cells rarely seen in people with other types of inflammatory arthritis. The findings are being presented at the virtual American College of Rheumatology/Association of Rheumatology Professionals annual meeting.

“Although checkpoint inhibitor-induced arthritis looks like other forms of inflammatory arthritis, our findings suggest that they’re not the same,” says study co-author Karmela Kim Chan, MD, a rheumatologist at HSS. “These findings are preliminary, but they are very interesting.”

Checkpoint inhibitor-induced arthritis occurs in about 5% of people taking immunotherapy drugs. The researchers looked at synovial fluid and blood from 10 cancer patients who had experienced this side effect; all of them were being treated with drugs that target the immune checkpoint CTLA-4 and/or PD-1. The team also analyzed blood and synovial fluid from 11 people with rheumatoid arthritis (RA) and nine people with spondyloarthropathies (SpA).

The analysis revealed a unique population of CD38^hiCD127^– CD8 T cells. This designation means that they expressed high levels of a marker called CD38 and did not express a marker called CD127. These T cells were expanded in both the blood and joint fluid of people with checkpoint inhibitor-induced arthritis.

Flow cytometry and RNA sequencing analysis demonstrated these cells to be both cytotoxic and actively proliferating.  Furthermore, RNA sequencing suggested that these cells may respond to the immune-related protein interferon, but more research is needed to confirm the significance.

“We don’t yet know if this population of T cells is causing checkpoint inhibitor-induced arthritis or if it’s a common feature of a larger population of people being treated with checkpoint inhibitor drugs,” notes Dr. Chan. “Our next step is study the blood and synovial fluid of more people being treated with these drugs and not limit our analysis only to those who are experiencing these side effects.”

She adds that eventually researchers may be able to develop drugs targeted to the T cells that cause joint inflammation, which could be used to treat this side effect.

Co-authors of this study include HSS rheumatologist Anne R. Bass, MD, and HSS scientist Laura Donlin, PhD.

About HSS

HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the 11th consecutive year), No. 4 in rheumatology by U.S. News & World Report (2020-2021), and named a leader in pediatric orthopedics by U.S. News & World Report “Best Children’s Hospitals” list (2020-2021). Founded in 1863, the Hospital has the lowest complication and readmission rates in the nation for orthopedics, and among the lowest infection rates. HSS was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center four consecutive times. The global standard total knee replacement was developed at HSS in 1969. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State, as well as in Florida. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. The HSS Global Innovation Institute was formed in 2016 to realize the potential of new drugs, therapeutics and devices. The HSS Education Institute is a trusted leader in advancing musculoskeletal knowledge and research for physicians, nurses, allied health professionals, academic trainees, and consumers in more than 130 countries. Through HSS Global Ventures, the institution is collaborating with medical centers and other organizations to advance the quality and value of musculoskeletal care and to make world-class HSS care more widely accessible nationally and internationally. www.hss.edu.