Causal relationship between inflammatory proteins, immune cells, and gout: a Mendelian randomization study

Abstract

Prior research has documented the association between certain circulating inflammatory proteins/immune cells and gout. However, the reliability of these associations remains contentious due to the constraints of conventional observational methodologies. This investigation seeks to reassess the causative link between circulating inflammatory proteins/immune cells and gout through the application of Mendelian randomization (MR). The study included 3576 individuals of European ancestry with gout, immune cell data from the GWAS summary of 3757 Sardinians, and circulating inflammatory protein data from 14,824 European ancestry participants for MR analysis. The principal approach employed was inverse variance weighted analysis to investigate the causal relationship between exposure and outcomes. The results indicate that CD28 on CD39+ CD4+ T cells may be associated with a reduced risk of gout. Additionally, CD45RA+ CD28- CD8bright T cells may also be associated with a reduced risk of gout. In contrast, DN (CD4-CD8-) T cells and IL-12β may increase the risk of gout. Some inflammatory proteins and immune cells show potential causal associations with gout. Nevertheless, additional experimental verification is warranted to assess the underlying mechanisms and confirm the causative role of these immune factors in gout pathogenesis.