Cytokine Signalling Forum


14-3-3eta is a novel mediator associated with the pathogenesis of rheumatoid arthritis and joint damage

Maksymowych WP, van der Heijde D, Allaart CF et al. - Arthritis Research and Therapy 2014, 16:R99

A major clinical imperative among rheumatologists is the ability to class patients into risk categories for radiographic progression. Indeed, identification of new independent biomarkers predictive of RA disease progression is a key target from OMERACT. This study by Maksymowych et al. sought to clarify the role of 14-3-3? in RA and whether it provided any clinically and/or serologically important prognostic information. First described as being elevated in RA in 2007, 14-3-3? has a strong correlation with matrix metalloproteinase (MMP) production, upregulation of which can lead to joint destruction.
Through various experiments it was noted that there was dose dependent induction of a range of inflammatory factors by 14-3-3?. Observed effects were similar to those noted at the same concentrations of TNFa. Induction of transcripts was evident at levels as low as 1ng/ml, the same concentration as found in RA patient serum.
14-3-3? also showed that it could be used as a biomarker for radiographic progression. 61% of early. RA patients who had 30 month follow up data (n=33) and 50% of patients with established RA (n=40) showed radiographic progression. In both of these groups, median 14-3-3? levels were higher in radiographic progression patients when compared with the non-progressing groups, although this was only significantly different in the early RA group.
This study has shown that a) 14-3-3?, at similar concentrations to TNFa, is capable of inducing genes previously described as being TNFa responsive and involved in promoting inflammation and b) 14-3-3? levels are higher in patients who demonstrate radiographic progression meaning it could be used as a new clinical biomarker. The results from this study are being used in the design of larger studies to formally investigate the merits of 14-3-3? as a new biomarker and provide rationale for investigation into whether 14-3-3? could be a new therapeutic target.