Synovial Tissue Analysis in the Pre-Clinical Phase of Arthritis: T-Cell Infiltration Preceding the Development of Arthritis

Maria J. H. de Hair¹, Marleen G. H. van de Sande¹, Tamara H. Ramwadhdoebe², Robert B. M. Landewé³, Christiaan van der Leij⁴, Mario Maas⁵, Dirkjan van Schaardenburg⁶, Danielle Marie Gerlag¹, Lisa G.M. van Baarsen² and Paul P. Tak⁷, ¹Division of Clinical Immunology and Rheumatology, Academic Medical Center / University of Amsterdam, Amsterdam, Netherlands, ²Division of Clinical Immunology and Rheumatology and Department of Experimental Immunology , Academic Medical Center / University of Amsterdam, Amsterdam, Netherlands, ³Division of Clinical Immunology and Rheumatology, Academic Medical Center / University of Amsterdam & Atrium Medical Center, Amsterdam, Netherlands, ⁴Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands, ⁵Department of Radiology, Academic Medical Center / University of Amsterdam, Amsterdam, Netherlands, ⁶Rheumatology, Jan van Breemen Research Institute | Reade, Amsterdam, Netherlands, ⁷Division of Clinical Immunology and Rheumatology, Academic Medical Center / University of Amsterdam and GlaxoSmithKline, Amsterdam, Netherlands

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: Arthroscopy, pathogenesis and rheumatoid arthritis, rheumatoid arthritis, Rheumatoid arthritis (RA), synovium, T cells

Session Information

Session Title: T-cell Biology and Targets in Autoimmune Disease

Session Type: Abstract Submissions (ACR)

Background/Purpose:

We have previously shown in a pilot study that there is no evident synovial inflammation in autoantibody-positive individuals who are at risk of developing rheumatoid arthritis (RA), compared to healthy controls. Here, we investigated in a larger, prospective cohort whether subtle changes in the synovium are associated with the development of clinically manifest arthritis in RA-prone individuals.

Methods:

Fifty-five IgM rheumatoid factor (RF) and/or anti-citrullinated protein antibody (ACPA) positive individuals, without evidence of arthritis upon physical examination who are at risk for developing RA, were included in the study. All individuals underwent MRI and arthroscopic synovial biopsy sampling of a knee joint at inclusion, and were prospectively followed for arthritis development. Biopsies were analysed by immunohistochemistry using antibodies for T cells (CD3, CD4, and CD8), B cells (CD22), fibroblast-like-synoviocytes (CD55), plasma cells (CD138), von Willebrand Factor and citrullinated fibrinogen. Proportional hazard regression analysis was performed to investigate associations of (combinations of) variables with onset of arthritis over time.

Results:

After a median follow-up time of 13 (IQR 6-27, range 1-47) months, 15 individuals (27%) developed arthritis. Synovial expression of CD3+ T cells was associated with arthritis development (Hazard ratio: 2.8; 95% confidence interval: (0.9 to 9.1; p=0.088)), although not statistically significant. Combined with ACPA-positivity CD3 expression was highly associated with arthritis development (double-positive vs. single-positive or double-negative (HR (95%CI): 4.0 (1.4 to 11.4); p=0.010)). The expression of other inflammatory cell markers as well as MRI-findings were not associated with arthritis development.

Conclusion:

The results presented here suggest that synovial T cell infiltration might play a role in arthritis development in autoantibody-positive individuals who are at risk of developing RA.

Disclosure:

M. J. H. de Hair,
None;

M. G. H. van de Sande,
None;

T. H. Ramwadhdoebe,
None;

R. B. M. Landewé,
None;

C. van der Leij,
None;

M. Maas,
None;

D. van Schaardenburg,
None;

D. M. Gerlag,
None;

L. G. M. van Baarsen,
None;

P. P. Tak,
None.

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