Systemic lupus erythematosus (SLE) is an autoimmune disease with multifactorial genesis. Recent research suggests a numerical and functional deficit of regulatory T (Treg) cells as an important contributing factor to the pathology seen in SLE. Treg cells play important roles in dampening overt stimulation of effector cells, as seen in many autoimmune diseases. As Treg cells are highly dependent on interleukin-2 (IL-2), application of low doses of IL-2 leads to markedly increased numbers and improved functionality of Treg cells in mice and humans. Several clinical trials investigated the safety of low-dose IL-2 treatment in different autoimmune diseases, including SLE. The trials conducted so far mainly focused on an increase in Treg cells after IL-2 treatment, not evaluating in detail the effects on other immune cells, presumably also playing important roles in the pathogenesis of SLE. For this reason, the investigators of this trial aim to conduct a complete phenotyping of cellular and soluble components in the blood of SLE patients treated with low-dose IL-2. Furthermore, the investigators want to offer this promising treatment to SLE patients in a controlled framework of an investigator initiated clinical trial.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
16
Subcutaneous injection of 1.5 million international units (MIU) of Aldesleukin (Proleukin®, Interleukin-2) once daily in 5-day courses every three weeks for a total of 4 cycles.
University Hospital Zurich
Zurich, Switzerland
Assessment of increase in percentage of Treg cells
The primary outcome of this study is an increase in percentage of Treg cells of total CD4+ T cells between visit 2 (baseline) and week 9 (visit 9) measured in the blood of SLE patients not receiving Belimumab treatment. Treg cells are defined as CD3+CD4+CD127loCD25hiFoxp3+ and total CD4+ T cells are defined as CD3+CD4+.
Time frame: Comparison between baseline (visit 2, day 0) and week 9 (visit 9, day 68).
Exploratory assessment of cellular immune cell subsets in the blood of SLE patients.
Different immune cell subsets isolated from whole blood will be quantified. Immune cells of interest will include: T cell subsets, including effector and regulatory CD4 and CD8 T cells, B cells, natural killer cells, innate lymphoid cells, dendritic cells, monocytes/macrophages, as well as eosinophil, basophil and neutrophil granulocytes and their respective subtypes including premature stages.
Time frame: Comparison between baseline (visit 2, day 0), visit 3 (day 5), visit 4 (day 21), visit 5 (day 26), visit 6 (day 42), visit 7 (day 47), visit 8 (day 63), visit 9 (day 68), visit 10 (day 96) and visit 11 (day 124).
Exploratory assessment of soluble cytokines in the blood of SLE patients.
Quantification of cytokines in the blood will include: common gamma chain cytokines, pro-inflammatory cytokines and anti-inflammatory cytokines.
Time frame: Comparison between baseline (visit 2, day 0), visit 3 (day 5), visit 4 (day 21), visit 5 (day 26), visit 6 (day 42), visit 7 (day 47), visit 8 (day 63), visit 9 (day 68), visit 10 (day 96) and visit 11 (day 124).
Exploratory assessment of soluble CD25 in the blood of SLE patients.
Soluble CD25 will be quantified in the serum of SLE patients.
Time frame: Comparison between baseline (visit 2, day 0), visit 3 (day 5), visit 4 (day 21), visit 5 (day 26), visit 6 (day 42), visit 7 (day 47), visit 8 (day 63), visit 9 (day 68), visit 10 (day 96) and visit 11 (day 124).
Exploratory assessment of antibodies in the blood of SLE patients.
Specific and unspecific antibodies will be quantified. This measurement will include Immunglobulin subclasses (IgA, IgG, IgD, IgM and IgE), anti-dsDNA, antinuclear, anti-Sm and anti-C1q antibodies.
Time frame: Comparison between baseline (visit 2, day 0), visit 3 (day 5), visit 4 (day 21), visit 5 (day 26), visit 6 (day 42), visit 7 (day 47), visit 8 (day 63), visit 9 (day 68), visit 10 (day 96) and visit 11 (day 124).
Exploratory assessment of complement activity in SLE patients.
Activity of complete and classical complement pathways will be determined.
Time frame: Comparison between baseline (visit 2, day 0), visit 3 (day 5), visit 4 (day 21), visit 5 (day 26), visit 6 (day 42), visit 7 (day 47), visit 8 (day 63), visit 9 (day 68), visit 10 (day 96) and visit 11 (day 124).
Assessment of immune cells with immunohistochemistry and immunofluorescence in skin biopsies (optional outcome)
Skin biopsies will be optional and only taken from patients signing a separate consent form.
Time frame: Comparison between baseline (visit 2, day 0) and week 9 (visit 9, day 68).
Clinical response measured by the SELENA-SLEDAI score.
Time frame: Comparison between baseline (visit 2, day 0), visit 5 (day 26), visit 9 (day 68) and visit 11 (day 124).
Clinical response measured by the BILAG-2004 score.
Time frame: Comparison between baseline (visit 2, day 0), visit 5 (day 26), visit 9 (day 68) and visit 11 (day 124).
Clinical response measured by the Physician's Global Assessment (PGA) score.
Time frame: Comparison between baseline (visit 2, day 0), visit 5 (day 26), visit 9 (day 68) and visit 11 (day 124).
Clinical response measured by the SLE Responder Index (SRI).
Time frame: Comparison between baseline (visit 2, day 0), visit 5 (day 26), visit 9 (day 68) and visit 11 (day 124).
Reduction in dosing of concomitant medication.
Time frame: Comparison between baseline (visit 2, day 0), visit 3 (day 5), visit 4 (day 21), visit 5 (day 26), visit 6 (day 42), visit 7 (day 47), visit 8 (day 63), visit 9 (day 68), visit 10 (day 96) and visit 11 (day 124).
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