title: Regulatory T Cell Responses to High-Dose Methylprednisolone in Active Systemic Lupus Erythematosus.
abstract: OBJECTIVE
  A slight increase in the proportion of circulating regulatory T (Treg) cells has been reported in systemic lupus erythematosus (SLE) patients taking oral prednisone. The effects of intravenous (IV) high dose methylprednisolone (MP) on Tregs have not yet been described, especially in active SLE.
  
  
  METHODS
  We prospectively analyzed the proportion of circulating CD4+ Treg cell subsets defined as follows: (1) naïve Treg (nTreg) FoxP3lowCD45RA+ cells; (2) effector Treg (eTreg) FoxP3highCD45RA- cells; and (3) non-suppressive FoxP3lowCD45RA- cells (non-regulatory Foxp3low T cells). Peripheral blood mononuclear cells of patients with active SLE were analyzed before the first infusion of IV high dose MP (day 0) and the following days (day 1, day 2, ±day 3 and ±day 8). The activity of SLE was assessed by the SLEDAI score.
  
  
  RESULTS
  Seventeen patients were included. Following MP infusions, the median (range) percentage of eTregs significantly increased from 1.62% (0.53-8.43) at day 0 to 2.80% (0.83-14.60) at day 1 (p = 0.003 versus day 0), 4.64% (0.50-12.40) at day 2 (p = 0.06 versus day 1) and 7.50% (1.02-20.70) at day 3 (p = 0.008 versus day 2), and declined to baseline values at day 8. Expanding eTreg cells were actively proliferating, as they expressed Ki-67. The frequency of non-regulatory FoxP3low T cells decreased from 6.39% (3.20-17.70) at day 0 to 4.74% (1.03-9.72) at day 2 (p = 0.005); nTreg frequency did not change. All patients clinically improved immediately after MP pulses. The absence of flare after one year of follow up was associated with a higher frequency of eTregs at day 2.
  
  
  CONCLUSIONS
  IV high dose MP induces a rapid, dramatic and transient increase in circulating regulatory T cells. This increase may participate in the preventive effect of MP on subsequent flares in SLE.
authors.affiliation: Service de médecine interne 2, Centre de Référence National pour le Lupus et le Syndrome des Antiphospholipides, institut E3M, Groupement Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, Inserm UMRS1135, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), 83 Bd de l'hôpital, F-75013, Paris, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Mathian
authors.affiliation: Service de médecine interne 2, Centre de Référence National pour le Lupus et le Syndrome des Antiphospholipides, institut E3M, Groupement Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, Inserm UMRS1135, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), 83 Bd de l'hôpital, F-75013, Paris, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Jouenne
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm UMRS1135, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), 83 Bd de l'hôpital, F-75013, Paris, France.|Département d'immunologie, Groupement Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Driss
authors.initials: D
authors.lastname: Chader
authors.affiliation: Service de médecine interne 2, Centre de Référence National pour le Lupus et le Syndrome des Antiphospholipides, institut E3M, Groupement Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Fleur
authors.initials: F
authors.lastname: Cohen-Aubart
authors.affiliation: Service de médecine interne 2, Centre de Référence National pour le Lupus et le Syndrome des Antiphospholipides, institut E3M, Groupement Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, Inserm UMRS1135, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), 83 Bd de l'hôpital, F-75013, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Haroche
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm UMRS1135, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), 83 Bd de l'hôpital, F-75013, Paris, France.
authors.forename: Jehane
authors.initials: J
authors.lastname: Fadlallah
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm UMRS1135, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), 83 Bd de l'hôpital, F-75013, Paris, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Claër
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm UMRS1135, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), 83 Bd de l'hôpital, F-75013, Paris, France.|Département d'immunologie, Groupement Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Musset
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm UMRS1135, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), 83 Bd de l'hôpital, F-75013, Paris, France.|Département d'immunologie, Groupement Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Gorochov
authors.affiliation: Service de médecine interne 2, Centre de Référence National pour le Lupus et le Syndrome des Antiphospholipides, institut E3M, Groupement Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, Inserm UMRS1135, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), 83 Bd de l'hôpital, F-75013, Paris, France.
authors.forename: Zahir
authors.initials: Z
authors.lastname: Amoura
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm UMRS1135, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), 83 Bd de l'hôpital, F-75013, Paris, France.|Département d'immunologie, Groupement Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Makoto
authors.initials: M
authors.lastname: Miyara
mesh_terms: D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D008775:Methylprednisolone