Increase of peripheral T regulatory cells during remission induction with cyclophosphamide in active systemic lupus erythematosus.

Abstract

BACKGROUND:

Cyclophosphamide 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 METHODS:

Ten 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/m(2) /month for 6 months); doses of other administered drugs, including steroids, remained stable or lower. CD4(+) CD25(high) FOXP3(+) 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).

RESULTS:

In 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.

CONCLUSIONS:

Cyclophosphamide pulse therapy was associated with a significant increase of the CD4(+) CD25(high) FOXP3(+) 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.

• Authors: Konstantinos Tselios, Alexandros Sarantopoulos, Ioannis Gkougkourelas, Aikaterini Papagianni, Panagiota Boura
• Journal: International journal of rheumatic diseases (Int J Rheum Dis) Vol. 17 Issue 7 Pg. 790-5 (Sep 2014) ISSN: 1756-185X [Electronic] England
• PMID: 25430593 (Publication Type: Journal Article)
• Copyright: © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Chemical References

• Biomarkers
• FOXP3 protein, human
• Forkhead Transcription Factors
• IL2RA protein, human
• Immunologic Factors
• Interleukin-2 Receptor alpha Subunit
• Cyclophosphamide

Topics

• Adult
• Biomarkers (blood)
• Cyclophosphamide (administration & dosage)
• Female
• Forkhead Transcription Factors (blood)
• Humans
• Immunologic Factors (administration & dosage)
• Interleukin-2 Receptor alpha Subunit (blood)
• Lupus Erythematosus, Systemic (blood, diagnosis, drug therapy, immunology)
• Lupus Nephritis (blood, diagnosis, drug therapy, immunology)
• Lupus Vasculitis, Central Nervous System (blood, diagnosis, drug therapy, immunology)
• Male
• Pulse Therapy, Drug
• Remission Induction
• T-Lymphocytes, Regulatory (drug effects, immunology)
• Time Factors
• Treatment Outcome
• Up-Regulation