Session Information
Session Title: Rheumamtoid Arthritis - Human Etiology and Pathogenesis
Session Type: Abstract Submissions (ACR)
Background/Purpose:
Stromal cells in synovial tissue (ST) of patients with arthritis may have an important role in the initiation and persistence of the inflammatory infiltrate. Previous studies showed increased expression of stromal markers in ST of patients with established rheumatoid arthritis (RA) (Maia et al, Arthritis Rheum 2010:62:3595; Ekwall et al, Arthritis Res Ther 2011:13:R40). Here we investigated the expression of CD248, gp38, CD55 and PDI in early arthritis in relationship to diagnosis and outcome. Furthermore, these markers were tested in the ST of individuals without clinically apparent arthritis who are at risk for developing RA.
Methods:
Forty-seven patients with early inflammatory arthritis (<1 year disease duration) and 19 IgM rheumatoid factor and/or anti-citrullinated peptide antibody (ACPA) positive individuals with arthralgia but without arthritis were included in this study. Of the latter group, 9 individuals developed arthritis after a mean follow-up time of 3.4 years. In the early arthritis cohort, patients were diagnosed at baseline and at 2 years follow up as gout (n = 10), psoriatic arthritis (PsA, n = 9), undifferentiated arthritis (UA-UA, n = 10), UA-RA (n = 4) and RA-RA (n = 14). Patients were also classified based on prognostic outcome after 2 years into self-limiting, persistent non-erosive and persistent erosive disease. Synovial tissue was obtained by miniarthroscopy and analyzed by immunofluorescence to detect CD248, gp38, CD55 and PDI on stromal cells.Slides were examined by confocal microscopy. Expression was quantified as pixel/um². Kruskal–Wallis test and Mann–Whitney U test were used for statistical analysis. A P-value <0.05 was considered statistically significant.
Results:
We observed clear expression of CD248, gp38, CD55 and PDI in ST of patients with early arthritis, independent of diagnosis or outcome (table 1). In the autoantibody positive subjects at risk of developing RA, the expression of gp38 was lower compared to early RA (p = 0.0025). Expression levels were not different between individuals who developed RA after follow up (n = 9) compared to those who did not (n = 10).
Conclusion:
The stromal cell markers CD248, gp38, PDI and CD55 are all expressed in the earliest stages of clinically manifest arthritis, independent of the diagnosis and outcome after follow up. In preclinical RA the expression of gp38 is lower compared to early RA. Stromal markers seem to be expressed in a stable way in the ST during the development from being at risk of RA to early RA.
Table 1. Median expression levels in early arthritis and preclinical RA
|
Median expression |
Expression levels in early arthritis in reationship to diagnosis |
Expression levels in early arthritis in relationship to outcome |
Expression levels in preclinical RA |
||||||||||
|
(in pixel/um²) |
Gout |
PsA |
RA-RA |
UA-RA |
UA-UA |
P* |
Erosive |
Non-erosive |
Self limiting |
P* |
Arthritis+ |
Arthritis- |
P* |
|
CD248 |
0.037 |
0.056 |
0.026 |
0.080 |
0.043 |
ns |
0.018 |
0.026 |
0.053 |
ns |
0.015 |
0.051 |
ns |
|
Gp38 |
0.007 |
0.030 |
0.008 |
0.003 |
0.009 |
ns |
0.010 |
0.008 |
0.005 |
ns |
0.000 |
0.000 |
ns |
|
CD55 |
0.014 |
0.027 |
0.014 |
0.017 |
0.006 |
ns |
0.016 |
0.011 |
0.016 |
ns |
0.017 |
0.019 |
ns |
|
PDI |
0.056 |
0.075 |
0.026 |
0.022 |
0.037 |
ns |
0.025 |
0.044 |
0.037 |
ns |
0.004 |
0.004 |
ns |
*ns: not significant, p-value ≥0.05
Arthritis +: Seropositive individuals who developed arthritis during follow-up time of 3.4 years
Arthritis -: Seropositive individuals who did not develop arthritis after a mean follow-up time of 3.4 years
Disclosure:
Y. K. Choi,
None;
O. N. Karpus,
None;
P. P. Tak,
Employee of GlaxoSmithKline,
3;
J. Hamann,
None;
C. D. Buckley,
None;
A. Filer,
None;
D. M. Gerlag,
None.
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