The influence of therapy on CD4+CD25highFOXP3+regulatory T cells in systemic lupus erythematosus patients: a prospective study

Objectives: Regulatory T cells (Tregs) are inversely correlated to disease activity in systemic lupus erythematosus (SLE). However, little is known concerning the influence of immunosuppressive agents on Tregs, which was the objective of this study. Method: Thirty-five patients with SLE (29 females, six males, mean age 42.4 +/- 12.8 years) were included. CD4+CD25(high)FOXP3+ Tregs were prospectively assessed by flow cytometry every month for intravenous (iv) and quarterly for oral regimens. Clinical assessment was made with the SLE Disease Activity Index (SLEDAI). Statistical analysis was performed with a Student's t-test; p < 0.05 was considered significant. Results: In total, 44 cases of SLE relapse were treated with iv cyclophosphamide (CYP, n = 10), iv methylprednisolone (MP, n = 7), iv immunoglobulins (IVIGs, n = 5), oral MP (n = 8), oral MP + azathioprine (AZA, n = 8), and hydroxychloroquine (HCQ, n = 6). CYP, iv MP, and IVIGs resulted in a significant increase in Tregs (4.2 +/- 1.6 vs. 10.1 +/- 5.7, 2.9 +/- 1.3 vs. 10.6 +/- 4.8, and 5.6 +/- 2.7 vs. 15.2 +/- 6.3 cells/mm(3), respectively, p < 0.05). Oral MP, alone or combined with AZA, led to a significant increase in Tregs (7.4 +/- 2.5 vs. 11.8 +/- 3.8 and 5.1 +/- 2.4 vs. 9.4 +/- 3.6 cells/mm(3), respectively, p < 0.05), as did HCQ (8.2 +/- 2.4 vs. 12.8 +/- 2.7 cells/mm(3), p < 0.05). Time to Tregs recovery was significantly shorter with iv MP and IVIGs compared to CYP (1.4 +/- 0.5, 1.6 +/- 0.9, and 4.0 +/- 1.5 months, respectively, p < 0.05). Conclusions: Increase in Tregs during SLE remission is independent of the therapeutic regimen used and probably represents an epiphenomenon of disease remission. Time to Tregs restoration was significantly shorter in patients treated with iv MP and IVIGs compared to CYP pulse therapy.