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
Authors: C. Von Spee-Mayer, E. Siegert, A. Rose, J. Humrich, G. Riemekasten
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> 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. <h3>Objectives</h3> 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. <h3>Methods</h3> 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). <h3>Results</h3> 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 <i>in vitro</i>. 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 patient9s disease activity and a remarkable decrease of anti-dsDNA antibody levels. <h3>Conclusions</h3> 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 <i>in vivo</i> 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. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5367