The disease formerly known as rheumatoid arthritis

Abstract

Rheumatoid arthritis is a complex disease where predetermined and stochastic factors conspire to confer disease susceptibility. In light of the diverse responses to targeted therapies, rheumatoid arthritis might represent a final common clinical phenotype that reflects many pathogenic pathways. Therefore, it might be appropriate to begin thinking about rheumatoid arthritis as a syndrome rather than a disease. Use of genetics, epigenetics, microbiomics,and other unbiased technologies will probably permit stratification of patients based on mechanisms of disease rather than by clinical phenotype.

Figure 1

Simplified schema showing how genes might affect clinical responses to targeted therapies. Various genes with associated single nucleotide polymorphisms (SNPs) could be generally categorized into various pathogenic mechanisms (for example, tumor necrosis factor (TNF), T cells, B cells, others in this version). A particular individual might only inherit a subset of each of these SNPs. If the majority of inherited SNPs cluster in one mechanism, such as TNF blocker (see bottom rows), then the individual would have a response to the agent that targets this pathway. If the SNPs are not enriched for any particular pathway, then the patient would be a nonresponder. This schema only focuses on SNPs, but would be integrated with pathways that are enriched for epigenetic marks or other regulators of gene expression/function.