Session Information
Title: Rheumatoid Arthritis - Clinical Aspects: Novel Biomarkers and Other Measurements of Disease Activity
Session Type: Abstract Submissions (ACR)
Background/Purpose The 14-3-3η protein has been described as a mechanistic marker that is detectable in serum during the very early stages of RA development. A specific anti-14-3-3η autoantibody response is present in RA serum and is postulated to be protective when it effectively clears systemic 14-3-3η. This study examined the baseline expression of 14-3-3η markers (protein and pan-autoantibodies) in a recent onset polyarthritis cohort and their association with the progression of joint damage.
Methods 335 subjects were evaluated; 40 DMARD-naïve patients from the Sherbrooke EUPA cohort and 295 controls. Median age was 50 yrs, 2 months median disease duration, 75% were female and 60% were positive for RF and 55% for ACPA. Controls included 106 healthy and 189 disease controls consisting of connective tissue disease, OA, AS or autoimmune disorders. 14-3-3η protein levels were previously tested in this cohort using the Augurex 14-3-3η ELISA (cut-off ≥0.19 ng/ml) and 50% of the recent onset polyarthritis patients were positive. 14-3-3η AAb levels were measured on the MSD ECL platform using an established positive cut-off ≥380 U/ml. The group that was 14-3-3η AAb-only positive, in whom the 14-3-3η protein would have been cleared, was compared to the remainder of the cohort in terms of differences in radiographic progression over 30 months using the Mann-Whitney U-test. The Fisher Exact test was used to determine the association between marker positivity and radiographic progression (SHS≥3 at 30 months).
Results Median (IQR) 14-3-3η AAb values were significantly higher in early RA 617 U/ml (473-742) vs all controls 264 U/ml (200-348), p<0.0001 delivering a ROC AUC of 0.89 (95%CI:0.85-0.94). When compared to healthy subjects, the ROC AUC was 0.95 (95%CI:0.92-0.99), p<0.0001 delivering 93% specificity and 85% sensitivity with a likelihood ratio (LR) of 11.3. Thirty-four patients (85%) were 14-3-3η AAb positive, 88% were positive for either of the 14-3-3η markers and a Pearson correlation between the two 14-3-3η markers of r < 0.01 highlighted their complementary nature. Of the 40 patients, 15 (38%) were only positive for the 14-3-3η AAbs and had significantly less joint damage progression at 30 months, median (IQR) ΔSHS 0 (0-3.5) vs the rest of the cohort, 5 (-0.3–11.5), p<0.03. The Fisher exact test revealed that 14-3-3η AAb positivity (in the absence of the 14-3-3η protein) is associated with less radiographic progression at 30 months yielding an Odds Ratio of 5.3 (95%CI 1.2-23.9). p=0.03.
Conclusion 14-3-3η and anti-14-3-3η biomarkers identify 88% of recent onset polyarthritis patients and those who are only positive for 14-3-3η AAbs have a more favorable radiographic prognosis. This is potentially due to the more effective clearance of deleterious 14-3-3η protein by anti-14-3-3η antibodies in these patients.
Disclosure:
G. Boire,
Augurex Life Sciences Corp,
5;
N. Carrier,
None;
A. J. de Brum-Fernandes,
None;
P. Liang,
None;
A. Masetto,
None;
Y. Gui,
Augurex Life Sciences Corp,
3;
M. Murphy,
Augurex Life Sciences Corp,
3;
W. P. Maksymowych,
Augurex Life Sciences Corp,
5;
A. Marotta,
Augurex Life Sciences Corp.,
3.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/88-of-recent-onset-polyarthritis-patients-are-positive-for-14-3-3%ce%b7-markers-and-14-3-3%ce%b7-auto-antibodies-inform-a-favourable-prognosis/