Artikel
Induction of clinical remission by low-dose IL-2 in two patients with refractory SLE
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Veröffentlicht: | 12. September 2014 |
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Gliederung
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Background: Interleukin-2 (IL-2) is crucial for the growth and survival of regulatory T cells (Treg), and thus for the control of autoimmunity. In previous studies we have proven a causal relationship between an acquired IL-2-deficiency, reversible defects in Treg biology and the development of systemic lupus erythematosus (SLE), providing the rationales for an IL-2-based immunotherapy of SLE in order to restore Treg activity an thus to resurrect endogenous mechanisms of tolerance that can counteract autoimmunity.
Here we report a rapid and robust reduction of disease activity in parallel to a remarkable expansion of the Treg population by an off-label therapy with low-dose IL-2 in two patients with a long-term history of SLE and increased disease activity refractory or intolerant to a large variety of approved and experimental therapies.
Methods: The therapeutic regimen consisted of four treatment cycles each with daily subcutaneous injections of IL-2 (aldesleukin; Proleukin®) at single doses between 1.5 and 3.0 million IU on five consecutive days separated by washout-periods of 9-16 days.
Results: In the first treated patient, disease activity, determined by the SELENA-SLEDAI, rapidly decreased already after one treatment cycle, while in the second patient a reduction in disease activity was observed two weeks later. During the following treatment cycles disease activity further decreased or remained low due to disappearance of clinical manifestations such as arthritis, myositis and skin rash. In addition and unexpectedly levels of anti-dsDNA-antibodies considerably declined in both patients. The clinical response was associated with cyclic and treatment-related increases of the CD25hiFoxp3+CD127lo Treg population in the peripheral blood. The therapy was very well tolerated and adverse events were generally mild and transient.
Conclusion: These data provide the first evidence for the clinical efficacy of low-dose IL-2-therapy in conjunction with the boosting of Treg activity in SLE and strongly support the rationales of this selective biological therapeutic strategy.