Background/Purpose

In RA, irreversible joint damage often begins within the first year of symptom onset. A compelling and growing body of data describing the “uncoupling” of inflammation and joint destruction indicates that radiographic monitoring is important in all RA patients, regardless of clinical response. C-reactive protein (CRP) is an acute phase reactant that is routinely used alongside clinical assessment to evaluate response to treatment in RA although ~30-40% of patients have normal levels. 14-3-3η is a modifiable serum/plasma mechanistic biomarker that is a potent regulator of MMP expression and its positive status in early RA predicts radiographic progression. This study examines 14-3-3η’s relationship with CRP in an early RA cohort and whether its baseline expression in CRP-normal patients relates to radiographic outcome at year 1.

Methods

Baseline serum 14-3-3η protein titres were measured in a cohort of 409 early RA patients from the Reade Institute; all patients were treatment naive at baseline. Median patient age was 56 years and 73% were female. Patient plasma was tested on the 14-3-3η ELISA (cut-off ≥0.19 ng/ml) and differences in joint damage progression over three years along 14-3-3η positive/negative status groups was evaluated within the whole cohort and between CRP-normal (≤10 mg/L) and elevated groups. Statistical analyses were performed (GraphPad Prism 5.0) using Spearman correlations to compare relationships between variables and the Mann-Whitney u-test to assess median differences between groups.

Results

67% of patients were positive for the 14-3-3η protein and 60% of patients had elevated CRP (> 10mg/L). The Spearman correlation of baseline CRP and 14-3-3η titres showed no relationship between the two variables (r= 0.06). Baseline CRP titres correlated with TSS at year 1 (r=0.17, p=0.0007) as well as the change in TSS from baseline to year 1 (r=0.17, p=0.0005) but not with baseline TSS. Patients who were 14-3-3η protein positive had more radiographic progression than 14-3-3η negative patients over years 1, 2 and 3; p-values = 0.006, 0.008 and 0.009, respectively (Table). In patients with normal CRP (≤10 mg/L), 14-3-3η positive patients (n=105) had a higher mean (SD) radiographic progression at year 1 of 1.4 (3.4) versus the 14-3-3η negative group (n=55), 0.7 (2.3), p<0.05.

Median (min-max)	14-3-3η Negativen	14-3-3η Positiven	p-value
SHS Y1	0 (0-3)131	1 (0-5)273	0.02
SHS Y2	1 (0-5)133	2 (0-8)271	0.02
SHS Y3	1.5 (0-6)128	3 (0-10)264	0.01
Δ SHS Y1	0 (0-1)131	0 (0-2)274	0.006
Δ SHS Y2	0 (0-2.5)133	1 (0-6)271	0.008
Δ SHS Y3	0 (0-4)127	2 (0-7)264	0.009

Conclusion

14-3-3η is a mechanistic joint damage marker that does not correlate with the acute phase reactant CRP in early RA. These two markers provide unique information to assist in the clinical management of RA patients informing the uncoupling of inflammation and joint damage.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/14-3-3%ce%b7-a-mechanistic-biomarker-that-supports-the-concept-of-uncoupling-of-inflammation-and-joint-damage/