RESEARCH - Abnormal T cell differentiation persists in patients with RA in clinical remission and predicts relapse

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Published Online First: 20 July 2007. doi:10.1136/ard.2007.073833

ls of the Rheumatic Diseases 2008;67:750-757

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EXTENDED REPORTS

Abnormal T cell differentiation persists in patients with rheumatoid

arthritis in clinical remission and predicts relapse

C H Burgoyne 1,2, S L Field 1,2, A K Brown 1,2, E M Hensor 3, A

English 1,2, S L Bingham 1,2, R Verburg 4, U Fearon 1,2, C A Lawson

1,2, P J Hamlin 5, L Straszynski 2, D Veale 1,2, P Conaghan 1,2, M A

Hull 2,5, J M van Laar 4, A Tennant 3, P Emery 1,2, J D Isaacs 1,2, F

Ponchel 1,2

1 Academic Unit of Musculoskeletal Disease, University of Leeds, Leeds, UK

2 Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK

3 Psychometric Laboratory, University of Leeds, Leeds, UK

4 Rheumatology Department, Leiden University Medical Center, Leiden,

The Netherlands

5 Centre for Digestive Diseases, Leeds General Infirmary, Leeds, UK

Objectives: An abnormal CD4+ T cell subset related to inflammation

exposure (inflammation-related cells, IRC) has been identified in

rheumatoid arthritis (RA). Patients with inflammatory and

non-inflammatory diseases were used to examine the relationship

between inflammation and this T cell subset in vivo.

Methods: Blood was collected from healthy controls and patients with

RA (active disease or in clinical remission), Crohn's disease and

osteoarthritis. IRC and chemokine receptors were quantified by flow

cytometry. Thymic activity and apoptotic factors were measured by

real-time polymerase chain reaction. Circulating cytokines were

measured by enzyme-linked immunosorbent assay. CXCR4 and SDF1 in

synovial biopsies were measured using immunohistochemistry.

Results: IRC were identified in patients with RA (p<0.0001) and

Crohn's disease (p = 0.005), but not in those with osteoarthritis. In

RA in remission, IRC persisted (p<0.001). In remission,

hyperproliferation of IRC was lost, chemokine receptor expression was

significantly lowered (p<0.007), Bax expression dropped significantly

(p<0.001) and was inversely correlated with IRC (rho = –0.755, p =

0.03). High IRC frequency in remission was associated with relapse

within 18 months (OR = 6.4, p<0.001) and a regression model predicted

72% of relapse.

Conclusions: These results suggest a model in which, despite the lack

of systemic inflammation, IRC persist in remission, indicating that

IRC are an acquired feature of RA. They have, however, lost their

hyper-responsiveness, acquired a potential for survival, and no longer

express chemokine receptors. IRC persistence in remission confirms

their important role in chronic inflammation as circulating precursors

of pathogenic cells. This was further demonstrated by much higher

incidence of relapse in patients with high IRC frequency in remission.

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http://ard.bmj.com/cgi/content/abstract/67/6/750?etoc

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