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OP0104 Low-Dose Interleukin-2 Therapy Caused Selective Expansion of Regulatory T Cells Together with RAPID Reduction of Disease Activity in A Patient with Severe Refractory Sle
  1. C. Von Spee-Mayer1,2,
  2. E. Siegert1,
  3. A. Rose1,2,
  4. J. Humrich1,
  5. G. Riemekasten1
  1. 1Rheumatology And Clinical Immunology, Charité University Hospital, Berlin
  2. 2German Rheumatism Research Center (DRFZ), Berlin, Germany

Abstract

Background SLE is characterized by the breakdown of immune tolerance towards nuclear autoantigens. Aberrant activation of autoreactive T and B cells leads to uncontrolled inflammation and production of autoantibodies ultimately resulting in severe autoimmunity with diverse clinical manifestations. Quantitative and qualitative aberrations of CD4+ Foxp3+ regulatory T cells (Treg) have been associated with systemic lupus erythematosus (SLE). In addition, impaired production of Interleukin-2 (IL-2), the essential cytokine for peripheral Treg homeostasis, has been described for SLE T cells. These observations provide a strong rationale for an IL-2 therapy to selectively expand Treg in order to re-establish tolerance in SLE.

Objectives In this study we aimed to investigate the effect of low-dose Aldesleukin (Proleukin ®), an analogue of human IL-2, on disease activity and its influence on CD4+Foxp3+CD127lo Treg in a SLE patient.

Methods An individual therapeutic trial with subcutaneously administered low-dose Aldesleukin was performed after written informed consent of a patient with severe SLE refractory to various other therapies. The patient received four treatment cycles, each consisting of daily injections of Aldesleukin on five consecutive days followed by wash-out periods of 9-16 days between the cycles. The Aldesleukin dose was increased from 1.5mio IU/day in the 1st cycle to 3mio IU/day in the 2nd cycle and reduced again to 1.5mio IU/day for the following cycles. Peripheral lymphocytes were analyzed before and after each treatment cycle by flow cytometry. The clinical response was evaluated by the SLE disease activity score (SLEDAI).

Results The frequency of peripheral Foxp3+CD127lo Treg cells among CD3+CD4+ T cells increased from 21% at baseline to approximately 50% during IL-2 treatment cycles and CD25 expression (MFI) of Treg was increased up to 6-fold. Proliferation, evaluated by expression of Ki67, was selectively induced in Treg as compared to conventional CD4+ Foxp3- T cells. The IL-2-induced CD25+ Treg were able to suppress autologous CD4+ Foxp3- T cells in vitro. In addition, proliferation and frequencies of CD3-CD56+ NK cells were augmented during IL-2 treatment. These observations were accompanied by rapid reduction of the patient's disease activity and a remarkable decrease of anti-dsDNA antibody levels.

Conclusions These data provide the first evidence for the clinical efficacy of low-dose IL-2 therapy in the treatment of SLE. The beneficial effect of low-dose IL-2 on SLE disease activity can most likely be attributed to the selective in vivo expansion of functional Foxp3+CD127loCD25++ Treg. The contribution of Treg and other leukocyte subsets, e.g. NK cells, will be evaluated in more detail in a recently initiated clinical study with low-dose Aldesleukin for the treatment of SLE.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.5367

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