title: 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.
  
  
  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.affiliation: Clinical Immunology Unit, 2nd Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Tselios
authors.forename: Alexandros
authors.initials: A
authors.lastname: Sarantopoulos
authors.forename: Ioannis
authors.initials: I
authors.lastname: Gkougkourelas
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Papagianni
authors.forename: Panagiota
authors.initials: P
authors.lastname: Boura
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005260:Female; D051858:Forkhead Transcription Factors / Q000097:blood; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D008181:Lupus Nephritis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D020945:Lupus Vasculitis, Central Nervous System / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D020551:Pulse Therapy, Drug; D012074:Remission Induction; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D007155:Immunologic Factors; D053645:Interleukin-2 Receptor alpha Subunit; D003520:Cyclophosphamide
keywords: T regulatory cells; cyclophosphamide; systemic lupus erythematosus