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The persistence of abnormal T-cell differentiation patterns predicts relapse in rheumatoid arthritis patients with controlled disease
Arthritis Research & Therapy volume 7, Article number: P47 (2005)
We previously demonstrated abnormal T-cell differentiation in rheumatoid arthritis (RA) and hyperproliferation of T cells in relation with inflammation. However, it is still not clear whether these T-cell dysfunctions are a primary feature of RA or are only secondary to inflammation. We therefore analysed RA patients in clinical remission in whom systemic inflammation was controlled.
Patients were defined as in remission when they had controlled disease, with no change of activity for at least 6 months, C-reactive protein below 15, no swollen or tender joints and on stable treatment. Relapse was defined as a change in disease activity sustained for at least 3 months, requiring or not a change in treatment. Flow cytometry was used to assess T-cell differentiation pattern in controls (n = 23), active RA (n = 28) and remission (n = 34). CD4+ T-cell proliferation assay in response to mitogen, IL-2, and antibody stimulation in eight paired blood samples for active and remission disease. Statistical analysis was used to seek clinical and laboratory correlate to differentiation abnormalities.
The abnormal differentiation patterns observed in active disease were maintained in remission. The first inflammation-associated subset was persistent. The second atypical subset was never observed in health, poorly represented in active disease but largely accumulated in remission. The hypreproliferation associated with the first subset was lost in remission and was therefore driven by inflammation. The second atypical subset was associated with profound hyporesponsiveness in both active and remission disease. Relapse occurred in 13 out of 32 patients within 12 months of follow-up. Relapse was associated with a higher frequency of the inflammation-related cells (P = 0.017). We proceeded to a complete analysis of factors that could predict relapse. Only rheumatoid factor positivity (P = 0.033) and possibly having nodules (P = 0.079) were associated with relapse. Using a regression analysis revealed that the frequency of inflammation related cells was highly significant in predicting relapse, being correct in 78% of cases (P = 0.025). Neither the presence of rheumatoid factor or nodule improved this model.
These results suggest that the hyperreactivity of the inflammatory subset is associated with disease activity; however, its persistence in the absence of inflammation suggests a primary defect possibly in activation-induced cell death. The second subset appear fairly inactive, but more work is necessary to fully characterise these cells. Its complete absence in health and accumulation in disease remission also suggests a primary defect in T-cell differentiation pathways in RA.
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Brown, A., Ponchel, F., Isaacs, J. et al. The persistence of abnormal T-cell differentiation patterns predicts relapse in rheumatoid arthritis patients with controlled disease. Arthritis Res Ther 7, P47 (2005). https://doi.org/10.1186/ar1568
- Rheumatoid Arthritis
- Rheumatoid Arthritis Patient
- Rheumatoid Factor
- Active Rheumatoid Arthritis
- Tender Joint