Mechanisms of Articular Inflammation and Joint Damage in Arthritis
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 disesases in clinical trials.
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.