Mechanism of joint inflammation

Clinical research
My group has performed several observational studies on patients with rheumatoid arthritis (RA). We also worked on the effectiveness of biological agents. My position as coordinator of a large collaborative European study allowed me to publish important results on this topic using data from different European national cohorts. I was also the principal investigator of the first head to head randomized clinical trial comparing two anti-cytokine therapies in RA. More recently I have also investigated the corticosteroid-sparing effect of biological agents in RA and the role of IL-18 in autoinflammatory diseases in clinical trials.

Basic research
The proinflammatory effects of IL-1 are regulated by two different natural inhibitors, IL-1 receptor antagonist (IL-1Ra) and IL-1 receptor type 2 (IL-1R2), a decoy receptor. My group has created different genetically modified mouse lines, including transgenic mouse lines for promoter studies, transgenic mice overexpressing IL-1Ra isoforms, cell-specific IL-1Ra knockout mice, and knockout mice deficient in one of the intracellular IL-1Ra isoform. These mice were used to understand the regulation of expression and biological function of IL-1Ra and IL-1R2, respectively. We have performed seminal work on the role of IL-33 and IL-36, other members of the IL-1. My group is currently working on the role of IL-18 in autoinflammatory diseases.

Specific Expertise

I have a dual expertise both in clinical research in autoimmune and inflammatory diseases as well as in cytokine biology. Regarding the first area, I have conducted as PI some clinical trials that had an important impact on the management of patients with inflammatory diseases. I was also involved in large observational studies, notably I was the coordinator of several European national registries to study the role of cytokine blockade in the management of rheumatoid arthritis.

I have also an expertise in IL-1 biology. My laboratory developed several genetic tools to explore the role of IL-1 cytokines in vivo. My laboratory has also 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