Reading Rheum

These studies underscore the potential importance of intracellular signaling in the pathogenesis of autoimmune disease. Traf1 mediates signal transduction through TNF receptors, and Stat 4 is a key transcription factor that transmits signals from pro-inflammatory cytokines including IL-12 and IL-23. Although there is compelling biologic data on the roles of these cytokines and complement in RA, these genetic studies are presented without any functional data. Future studies will therefore need biochemical evaluation of the influence of these variants on protein expression and function. These studies also provide intriguing hints to overlapping mechanisms in diseases like RA and SLE, which have both distinctive and mutual features. However, whether the propensity to generate specific autoantibodies (i.e. anti–CCP) is genetically determined remains to be fully elucidated. Eventually, the use of individual genetic profiles could lead to customized treatment to target defective or overactive pathways to maximize efficacy and minimize side effects.

References

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