Increase of peripheral T regulatory cells during remission induction with cyclophosphamide in active systemic lupus erythematosus
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AbstractBackgroundCyclophosphamide efficacy in lupus nephritis (LN) and neuropsychiatric systemic lupus erythematosus (NPSLE) is probably mediated by a non‐specific ablation of reactive lymphocytes. However, little is known in regard to its effect on T regulatory cells (Tregs) in such patients, which was the aim of this study.Patients and MethodsTen Caucasian lupus patients were included, six with LN classes IV–V (mean age 33.8 ± 8.8 years) and four with NPSLE (mean age 35.5 ± 8.8 years, clinical manifestations: 1/4 acute confusional state, 1/4 psychosis, 2/4 refractory seizures). Cyclophosphamide was administered at monthly pulses (500 mg/m2/month for 6 months); doses of other administered drugs, including steroids, remained stable or lower. CD4+CD25highFOXP3+ Tregs were assessed by flow‐cytometry at baseline and before every subsequent pulse and 3–6 months after the final pulse. Disease activity was assessed by SLE Disease Activity Index (SLEDAI).ResultsIn LN patients, Tregs were significantly increased even after the fourth pulse (0.54 ± 0.20% vs. 1.24 ± 0.29%, P < 0.001). Likewise, in NPSLE, Tregs were significantly expanded after the fourth pulse (0.57 ± 0.23% vs. 1.41 ± 0.28%, P < 0.001). SLEDAI was significantly reduced in all patients.ConclusionsCyclophosphamide pulse therapy was associated with a significant increase of the CD4+CD25highFOXP3+ Tregs in patients with active LN and NPSLE. This effect is probably indirect and may partially explain the beneficial role of cyclophosphamide in such cases.
