The investigators have demonstrated that the mean percentage of circulating CD8+ regulatory T (CD8 Tregs) cells is significantly higher in patients with warm hemolytic anemia (wAHAI) in remission than in controls and is correlated to hemoglobin levels. In vitro, low dose of interleukine-2 (IL2) induce the expansion of CD8 Tregs. The objective is to demonstrate that, over a 9 week treatment period; low doses of IL2 can induce the expansion of CD8Tregs in patients with active wAHAI.
wAIHA is a B-cell-mediated autoimmune disease in which red blood cells are targeted by autoantibodies, which leads to marked decrease in their lifespan. The investigators demonstrated two years ago in a multivariate retrospective study that the CD3+CD8+ HLA-DR+ T-cell population was associated to a better outcome. The investigators observed that the proportion of circulating CD3+CD8+CD25highFoxp3+ T cells was significantly higher in patients with wAIHA in remission than in controls and correlated to hemoglobin levels. Extensive phenotyping and functional analysis revealed that those cells were bona fide Tregs acting in an IL10-dependent manner. Finally, culture of PBMC from normal donors or active wAIHAI patients with low dose of IL2 promoted the expansion of functional CD3+CD8+CD25+Foxp3+. Those observations constituted the rationale to propose low dose of IL2 to treat patients with active wAIHA with the objective of demonstrating that this treatment is able to induce the expansion of CD8Tregs, over a 9 week treatment period. Four courses of IL2 (aldesleukin \[Proleukin, Novartis\]) will be administered subcutaneously for 5 days. The first course will be limited to a dose of 1.5 million IU per day and followed by a 9 day wash-out. The other courses of 3 million IU per day will be initiated after a 16 day wash-out. Patients will be evaluated on day 1 and day 5 of each treatment course, before the first and last administration of interleukin-2 and will also be evaluated at 6 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Four courses of IL2 ( \[Proleukin, Novartis\]) will be administered subcutaneously for 5 days. The first course will be limited to a dose of 1.5 million IU per day and followed by a 9 day wash-out. The other courses of 3 million IU per day will be initiated after a 16 day wash-out.
CHU de Bordeaux Hôpital Haut Lévêque
Pessac, Aquitaine, France
Percentage of LTCD8+CD25highFoxp3+ .
Increase of the percentage of LTCD8+CD25highFoxp3+ at the end of the IL2 treatment.
Time frame: 9 weeks after inclusion
Incidence of complications with the treatment.
Safety of the treatment during the trial and 6 months after the inclusion
Time frame: 6 months after inclusion
Hemolysis as measured by hemoglobin, haptoglobin, reticulocytes and LDH levels
Impact of IL2 on hemolysis defined by hemoglobin, haptoglobin, reticulocytes, LDH levels
Time frame: 5 days, 20 days, 40 days, 61 days, 63 days and 6 months after inclusion
Evaluation of lymphocyte sub-populations
Impact of IL2 on lymphocyte sub-populations (NK cells, B lymphocyte, CD4T lymphocyte, CD8T lymphocytes, CD4Tregs levels) at each time point of evaluation.
Time frame: 5 days, 20 days, 40 days, 61 days, 63 days and 6 months after inclusion
Evaluation of lymphocyte activation.
Impact of IL2 on lymphocyte activation defined by DR expression at each time point of evaluation.
Time frame: 5 days, 20 days, 40 days, 61 days, 63 days and 6 months after inclusion
Dose of steroid treatment
Impact of IL2 on steroid treatment (dose) during the trial and 6 months after the inclusion
Time frame: 5 days, 20 days, 40 days, 61 days, 63 days and 6 months after inclusion
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Enrollment
2