RT Journal Article
SR Electronic
T1 Abnormal T cell differentiation persists in patients with rheumatoid arthritis in clinical remission and predicts relapse
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 750
OP 757
DO 10.1136/ard.2007.073833
VO 67
IS 6
A1 C H Burgoyne
A1 S L Field
A1 A K Brown
A1 E M Hensor
A1 A English
A1 S L Bingham
A1 R Verburg
A1 U Fearon
A1 C A Lawson
A1 P J Hamlin
A1 L Straszynski
A1 D Veale
A1 P Conaghan
A1 M A Hull
A1 J M van Laar
A1 A Tennant
A1 P Emery
A1 J D Isaacs
A1 F Ponchel
YR 2008
UL http://ard.bmj.com/content/67/6/750.abstract
AB 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.