CD8 and CD4 T Cells Associated with Active Disease Refractory to Anti-TNF Therapy in RA


“The role of terminally differentiated T effector memory re-expressing Temra in RA pathogenesis and disease activity is still unclear," investigators stated.

An increased frequency of CD4 and CD8 T cells was linked to disease activity in patients with rheumatoid arthritis (RA) receiving anti-tumor necrosis factor (anti-TNF) therapy, but not for patients taking disease-modifying antirheumatic drugs (DMARDs), such as abatacept and methotrexate, according to data presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress. CD4 Temra increased in patients who flared while tapering anti-TNF, indicating that CD45RA (Temra) may play a role in persistent disease activity in these patients.

“Highly differentiated T cells have been reported to be enriched in RA compared to healthy individuals,” investigators stated. “The role of terminally differentiated T effector memory re-expressing Temra in RA pathogenesis and disease activity is still unclear, including whether they can be used as a marker of sustained disease activity in RA patients receiving anti-TNF therapy.”

Patients with RA on anti-TNF therapy were recruited from a rheumatology clinic and were classified based on disease activity, with remission defined as no swollen joints, no C-reactive protein (CRP) of >5mg/L, no recorded Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP) ≥2.4, and were currently receiving a stable DMARD dose with no flare or loss of remission within the last 6 months. Clinical data and whole blood samples were collected. Patients receiving DMARDs, as well as healthy controls, were placed in comparison groups. Separately, a cohort of patients receiving anti-TNF therapy who were in remission and not receiving corticosteroids for 6 or more months were also recruited. Whole blood samples were taken prior to dose tapering as well as during flare. Peripheral blood mononuclear cells (PBMC) were obtained via gradient centrifugation of whole blood. Unadjusted values, analysis of variance (ANOVA) of log-transformed data, and Spearman’s rank correlations were used to attain unadjusted values, age-adjusted values, and the correlation between Temra and CRP, respectively.

A total of 36 patients with RA receiving anti-TNF, 12 patients receiving abatacept, 16 patients receiving methotrexate monotherapy, as well as 14 controls, were included in the study. A higher percentage of CD4 (age-adjusted p = 0.004) and CD8 Temra (age-adjusted p = 0.0007) patients with RA receiving anti-TNF therapy had persistent disease activity when compared with those who were in remission. Differences were validated after analyzing absolute numbers of CD4 and CD8 Temra. Surprisingly, there was no difference in Temra frequency between patients with RA in remission and non-remission in patients treated with methotrexate or abatacept.

Median Temra frequencies in patients with RA in remission were comparable to the control cohort. Additionally, Temra did not increase with age in the anti-TNF, methotrexate, or abatacept cohorts when compared with healthy individuals. CD4 and CD8 Temra were only associated with CRP in patients on anti-TNF therapy (CD4 Temra Spearman r = 0.5185, p = 0.001, and CD8 Temra Spearman r = 0.5040, p = 0.005). An increase in CD4 Temra (p = 0.003) was seen at the 3-month mark in patients who flared while tapering anti-TNF when compared with those in remission. However, an increase in CD8 Temra was not reported.

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