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Abstract Number: 408

14-3-3η Auto-Antibody Positivity Informs Better Clinical Outcomes in RA

D. van Schaardenburg1, Mairead Murphy2, Samina Turk3, Walter P. Maksymowych4 and Anthony Marotta5, 1Jan van Breemen Research Institute, Amsterdam, Netherlands, 2Augurex Life Sciences Corp., North Vancouver, BC, Canada, 3Reade, Amsterdam, Netherlands, 4University of Alberta, Edmonton, AB, Canada, 51423 Dempsey Road, Augurex Life Sciences Corp., North Vancouver, BC, Canada

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: ACPA, autoantibodies and joint damage, Early Rheumatoid Arthritis, Rheumatoid Factor

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Session Information

Session Title: Rheumatoid Arthritis - Clinical Aspects: Novel Biomarkers and Other Measurements of Disease Activity

Session Type: Abstract Submissions (ACR)

Background/Purpose We have previously reported pilot data that patients who are only positive for 14-3-3η auto-antibodies (AAb) and negative for the 14-3-3η protein have a lower radiographic trajectory over 3 years. 14-3-3η AAbs have been described as “protective” based on their currently understood mechanism of clearing “harmful” extracellular 14-3-3η protein. In this study, we investigated how 14-3-3η AAb plasma expression informs clinical variables at baseline and over 3 years in a substantial cohort of patients with early RA.

Methods Baseline serum 14-3-3η protein and AAb levels were measured in a cohort of 409 early RA patients; all patients were treatment naive at baseline. Median patient age was 56 years and 73% were female. 14-3-3η protein levels were tested using the Augurex 14-3-3η ELISA (cut-off ≥0.19 ng/ml) and 67% of patients were positive. 14-3-3η AAb levels were measured on the MSD ECL platform and using a diagnostic cut-off of 380 U/ml, 77% of patients were +ve. Patients were grouped into 4 groups: 1) Negative for both markers, 2) Positive for the 14-3-3η protein only, 3) Positive for the 14-3-3η AAb only and 4) Positive for both markers. Assessment of differences across these 4 groups was performed using Kruskal-Wallis Analysis of Variance (ANOVA) with Dunn’s post-hoc testing to identify differences between individual groups.

Results Across the four 14-3-3η biomarker expression groups (table), ANOVA revealed  significant differences in RF and CCP positive rates and titers (p<0.0001), baseline TSS, SJC28 and ESR (≤0.01). Patients who were only 14-3-3η auto-antibody positive had significantly lower positivity rates and titers of RF and CCP (p<0.0001).

 

ANOVA

(4 groups)

Double –

Protein +

AAb+

Double +

P-value

Baseline

 

 

 

 

 

 

RF +

< 0.0001

14%

81%

34%

79%

< 0.0001

CCP +

< 0.0001

41%

79%

35%

87%

< 0.0001

SJC28

0.0007

7

7

9

7

0.0002

ESR

0.02

18

27

31

32

NS

Over the 3 years, 14-3-3η auto-antibody +ve patients had significantly lower radiographic progression compared to patients who were double positive (p=0.004). 14-3-3η auto-antibody +ve patients also had significantly greater changes in response to treatment in SJC28 (p=0.0004) and DAS28 (0.006) compared to the double positive patient group.

Conclusion At baseline, the combination of a positive 14-3-3η auto-antibody test and a negative 14-3-3η protein test is significantly associated with a less severe RA disease profile and a better prognosis in regards to radiographic progression, SJC and DAS outcomes at 3 years. This data supports a protective role for 14-3-3η auto-antibodies.

 


Disclosure:

D. van Schaardenburg,

Augurex Life Sciences Corp,

5;

M. Murphy,

Augurex Life Sciences Corp,

3;

S. Turk,
None;

W. P. Maksymowych,

Augurex Life Sciences Corp,

5;

A. Marotta,

Augurex Life Sciences Corp.,

3.

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