Background Cyclophosphamide has been proved to be efficacious in remission induction in lupus nephritis (LN) and neuropsychiatric systemic lupus erythematosus (NPSLE), probably by a non-specific ablation of reactive lymphocytes. However, little is known in regard to its effect on T regulatory cells (Tregs).
Objectives Objective of this study was to investigate the influence of cyclophosphamide pulse therapy on the CD4+CD25highFOXP3+ Tregs in patients with active LN and NPSLE.
Methods Ten Caucasian lupus patients (selected from a cohort of 200 lupus patients followed up regularly in our Unit) were included. Six patients had active LN class IV-V (mean age 33.8±8.8 years, mean disease duration 87.2±63.4 months, mean proteinuria level 2576±3985mg/24h) and 4 active NPSLE (mean age 35.5±8.8 years, mean disease duration 103.8±55.1 months; clinical manifestations: 1/4 acute confusional state, 1/4 psychosis, 2/4 refractory seizures). Cyclophosphamide was administered at monthly pulses (500mg/m2/month for six months), while doses of all other administered drugs, including steroids, remained stable or lower throughout the study. CD4+CD25highFOXP3+ Tregs were assessed by flow cytometry at baseline and before every subsequent cyclophosphamide pulse and 3-6 months after the final pulse. Disease activity was assessed by SLE Disease Activity Index (SLEDAI).
Results In LN patients, Tregs were gradually increased from pulse to pulse. This increment reached statistical significance after the 4th pulse (0.54±0.20% vs. 1.27±0.32%, p<0.001), while SLEDAI was significantly decreased (15.2±6.8 vs. 2±1.6, p<0.001), along with proteinuria (2576±3985mg/24h to 234±86mg/24h, p<0.001). Likewise, in NPSLE, Tregs were significantly increased after the 4th pulse (0.57±0.23% vs. 1.41±0.28%, p<0.001) with a parallel SLEDAI reduction (17.8±7.7 vs. 2.1±1.6, p<0.001).
Conclusions Cyclophosphamide pulse therapy leads, over time, to a significant increase of the CD4+CD25highFOXP3+ Tregs in patients with active LN and NPSLE. Although this effect is probably indirect, it may partially reflect the restoration of lost tolerogenicity through the suppressive effect of cyclophosphamide on autoreactive lymphocytes.
Disclosure of Interest None Declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.