Adipose Inflammation and HLA-Obesity Interactions in Psoriatic Arthritis

Higher body mass index, a surrogate for adiposity, has been strongly linked to psoriatic arthritis risk and disease manifestations. In addition, treatment responses are blunted in psoriatic arthritis patients who are overweight or obese. Together, these findings suggest a mechanistic role for adipose tissue in the pathobiology of psoriatic arthritis. Activated macrophages and T cells, and their associated cytokines, contribute to the disease manifestations of psoriatic arthritis. Similarly, cellular infiltration of adipose tissue macrophages accompanies fat gain, with T-cells and other immune cells present and contributing to inflammatory function. Despite these compelling links, no studies have explored direct measures of adiposity in psoriatic arthritis, and none have yet evaluated adipose tissue inflammatory features in psoriatic arthritis in relation to disease manifestations and treatment responses. Additionally, inheritance of certain HLA-B and C alleles is associated with specific phenotypic manifestations of psoriatic arthritis, the penetrance of which may be conditioned on an individual's level of adiposity. However, these gene-obesity interactions have received little prior investigation. For this project, we will: 1) Compare measures of adipose inflammation, from tissue obtained from periumbilical subcutaneous adipose aspiration, between patients with psoriatic arthritis, rheumatoid arthritis, and controls without rheumatic diseases and evaluate the associations of adipose inflammatory tissue characteristics and metabolism with psoriatic arthritis phenotypic characteristics. 2) Quantify the effects of adipose partitioning and adipose tissue inflammation on treatment response in psoriatic arthritis. 3) Examine the interactions of adiposity and candidate HLA-B and C alleles and haplotypes on phenotypic characteristics of psoriatic arthritis using two well characterized Northern European psoriatic arthritis cohorts comprising over 500 psoriatic arthritis patients. Psoriatic arthritis is one of the most common forms of inflammatory arthritis. Its manifestations can be severe and disabling, and affected individuals often have a reduced lifespan and a lower quality of life. Understanding how adipose tissue contributes to these manifestations of psoriatic arthritis may identify novel targets for intervention to allow psoriatic arthritis patients live longer, happier, and more productive lives.