THE OFFICIAL NEWS SOURCE OF ACR CONVERGENCE 2022 • NOVEMBER 10-14



Ongoing T cell subset research has practical implications for rheumatology

R. John Looney, MD
R. John Looney, MD

Advances in immunology research continue to open new doors for rheumatologists.

During a state-of-the-art lecture Tuesday, R. John Looney, MD, will highlight recent advances and bring attendees up-to-date on the literature regarding T cell subsets and the practical implications this research has for rheumatology.

The symposiumImmunology Update: Therapeutic Targeting of T Cell Subsets will take place from 9:00 – 10:00 am on Tuesday in Room 29 D.

“One of the fun things in recent decades is how immunology research has been translated into clinical rheumatology,” Dr. Looney said. “We started out not having much immunology in rheumatology at all. Now we have amazing tools to look at the immune system. We still have a lot of diseases where we haven’t had as big of wins as we’d like, so we still have a long way to go. Nevertheless, it’s an exciting time.”

Dr. Looney, the Dr. Stephen I. Rosenfeld and Elise A. Rosenfeld Distinguished Professor in Allergy and Clinical Immunology in the Department of Medicine at the University of Rochester Medical Center, Rochester, NY, will begin with a review of the major T cell subsets and pathways of differentiation and homing to provide a framework for discussing T cell-directed therapies.

“Today, rheumatologists probably need to have an understanding of at least five T cell subsets to stay on top of what’s going on in the literature and clinically,” he said. “There are some treatments targeting T cell subsets that haven’t worked out. For example, trials of anti-interferon gamma didn’t go anywhere. However, there have been some really big successes targeting Th2 cells for allergy and targeting Th17 cells in auto-immune disease.”

Dr. Looney’s lecture mostly will focus on Th17 cells and their related variants.

“We’ve really seen a blossoming of research in this area,” he said. “I want to highlight some of the successes of targeting IL-17 and IL-23, but also talk about some of the failures. I want to help rheumatologists understand why for some of the diseases we’re most interested in, such as rheumatoid arthritis, we haven’t seen the kind of impact that we’ve been hoping to see with anti-IL-17.”

He’ll then talk about where research is headed.

“There’s some exciting approaches on the horizon,” Dr. Looney said. “Bispecific antibodies is one example. Anti-TNF/anti-IL-17 bispecific antibodies may be particularly effective for synovitis. Induction of specific regulatory T cells in animal models via immunization with nanoparticle MHC peptide complexes or micro particles containing antigen and rapamycin has produced remarkable results but still needs translation into human disease.”

Dr. Looney also said research will likely continue to reveal unknown T cell subsets.

“There’s data that’s come out in the past year that suggests that there may be additional T cell subsets, and they may point us toward new targets for future therapies,” he said. “As new therapies are developed, it will be necessary to be able to talk about these cells and to understand how they work.”

Dr. Looney will also emphasize the importance of understanding how new therapies may be beneficial for some diseases but have other unintended implications.

“What is the implication when you target Th17 cells? What other diseases might you precipitate if you give these drugs? What adverse events might you expect?” he asked. “For example, some of these cells are designed to fight certain types of fungal infections, including candida and staph aureus infections. So patients using these types of therapies may be at higher risks for these infections.”

Rheumatologists may not treat atopic dermatitis or asthma, Dr. Looney said, but they need to be aware of a drug that seems to be successful for these conditions — dupilumab, which blocks IL-4 and IL-13.

“There’s pretty good evidence that IL-4 blocks some of the adverse effects of the T cells that are important in rheumatic disease,” he said. “Th17 cells are very important for bone erosions. Probably the most important cell for determining if you have erosive disease or not. And the Th2 cells that you target with this drug for atopic dermatitis and asthma are blocked by the drug. So if you have a patient on methotrexate, and they’re put on dupilumab for asthma, their rheumatoid arthritis might get much worse.”