Mechanism of joint inflammation
CLINICAL RESEARCH
Prof. Gabay has conducted several observational studies on patients with rheumatoid arthritis (RA), with a particular focus on the effectiveness of biological agents. As coordinator of a large collaborative European study, he published significant findings using data from various national cohorts across Europe. He also served as the principal investigator of the first head-to-head randomised clinical trial comparing two anti-cytokine therapies in RA. More recently, he has explored the corticosteroid-sparing effects of biological agents in RA and investigated the role of IL-18 in autoinflammatory diseases through clinical trials.
BASIC RESEARCH
Prof. Gabay's research has contributed extensively to understanding the regulation of proinflammatory cytokines, particularly interleukin-1 (IL-1). His group has studied the two natural inhibitors of IL-1—IL-1 receptor antagonist (IL-1Ra) and IL-1 receptor type 2 (IL-1R2), a decoy receptor. His team developed a range of genetically modified mouse models, including transgenic lines for promoter studies, mice overexpressing IL-1Ra isoforms, cell-specific IL-1Ra knockout mice, and mice deficient in intracellular IL-1Ra isoforms. These models have been instrumental in elucidating the regulation and biological roles of IL-1Ra and IL-1R2. Prof. Gabay’s group has also made seminal contributions to the understanding of IL-33 and IL-36, members of the IL-1 cytokine family. His current research focuses on the role of IL-18 in autoinflammatory diseases.
SPECIFIC EXPERTISE
He has a dual expertise, both in clinical research in autoimmune and inflammatory diseases as well as in cytokine biology. Regarding the first area, he has conducted as PI some clinical trials that had an important impact on the management of patients with inflammatory diseases. He was also involved in large observational studies, notably, he was the coordinator of several European national registries to study the role of cytokine blockade in the management of rheumatoid arthritis.
He also has expertise in IL-1 biology. His laboratory developed several genetic tools to explore the role of IL-1 cytokines in vivo. They also have a vast expertise in various experimental models of inflammatory diseases, including arthritis, psoriasis, and macrophage activation syndrome.
SELECTED PUBLICATIONS
Gabay C., Smith Jr. M. F., Eidlen D., Arend W.P.: Interleukin 1 receptor antagonist is an acute-phase protein. J Clin Invest 1997; 99: 2930-40
Vigne S., Palmer G., Martin P., Lamacchia C., Strebel D., Rodriguez E., Olleros M.L., Vesin D., Garcia I., Ronchi F., Sallusto F., Sims J.E., Gabay C.: IL-36 Signaling Amplifies Th1 Responses by Enhancing Proliferation and Th1 Polarization of Naïve CD4+ T cells. Blood 2012; 120: 3478-87
Girard-Guyonvarc’h C., Palomo J., Martin P., Rodriguez E., Troccaz S., Palmer G., Gabay C.: Unopposed IL-18 signaling leads to severe TLR9-induced macrophage activation syndrome in mice. Blood 2018; 131: 1430-1441
Gabay C., Emery P., van Vollenhoven R., Dikranian A., Alten R., Pavelka K., Klearman M., Musselman D., Agarwal S., Green J., Kavanaugh A.: Tocilizumab monotherapy is Superior to adalimumab monotherapy in reducing disease activity in patients with rheumatoid arthritis (ADACTA) : results from a randomized double-blind trial. Lancet 2013; 381: 1541-1550
Gabay C., Fautrel B., Rech J., Spertini F., Feist E., Kötter I., Morel J., Schaeverbeke T., Hamidou M.A., Martin T., Hellmich B., Lamprecht P., Schulze-Koops H., Courvoisier D.S., sleight A., Schiffrin E.J.: Open-label muticenter, dose-escalating phase II clinical trial on the safety and efficacy of tadekinig alfa (IL-18BP) in adult-onset Still’s disease. Ann Rheum Dis 2018; 77: 840-847
6 Nov 2020