Barath, S. et al. The severity of systemic lupus erythematosus negatively correlates with the increasing number of CD4+CD25highFoxP3+ regulatory T cells during repeated plasmapheresis treatments of patients. Autoimmunity 40, 521-528

3rd Department of Internal Medicine, University of Debrecen, Debrecen, Hungary.
Autoimmunity (Impact Factor: 2.71). 12/2007; 40(7):521-8. DOI: 10.1080/08916930701610028
Source: PubMed


Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by increased pathologic autoantibody production. A decrease in the number of CD4+CD25(high)FoxP3+ regulatory T cells can play a key role in the loss of tolerance to self antigens. Our aim was to determine the absolute number of peripheral CD4+CD25(high)FoxP3+ T cells in 44 patients with SLE, furthermore, to measure the changes in the number of CD+CD25(high)FoxP3+ T cells in 5 patients with severe SLE treated with repeated plasmapheresis for 4-6 days in comparison to the changes in the activity of disease (SLEDAI). Percent of CD4+CD25(high)FoxP3+ T cells were measured by flow cytometry. The absolute number of peripheral CD4+CD25(high)FoxP3+ T cells was significantly decreased in the 44 patients with SLE compared to the healthy controls n = 32 (0.012 +/- 0.006 vs. 0.038 +/- 0.017 G/L, p < 0.05). In the 5 patients with severe SLE the repeated plasmapheresis treatments increased the peripheral number of CD4+CD25(high)FoxP3+ T cells. As the number of CD4+CD25(high)FoxP3+ T cells increased during the treatment, the activity of disease (the value of SLE activity index) decreased. In the peripheral blood of SLE patients not only the ratio was decreased (as it was published earlier) but also the absolute number of these regulatory T cells. The repeated plasmapheresis treatments of SLE patients induced a significant increase in the number of peripheral CD4+CD25(high)FoxP3+ T cells in parallel to the decrease in the values of SLEDAI (the activity of disease). This phenomenon is, among others, possibly due to the elimination of interpheron-alpha and lymphocytotoxic antibodies during plasmapheresis.

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    • "The rationale of plasma exchange is based on the rapid removal of circulating pathogenic autoantibodies, immunoglobulins, immune complexes, and toxins. One study showed a significant elevation of peripheral CD4+ CD25 high FoxP3+ suppressor T cells in SLE patients treated with repeated plasmapheresis resulting in significant clinical improvements, thereby suggesting the increase in regulatory T cells may be one of the reasons of the beneficial effects of plasmapheresis in SLE patients [111]. Rituximab, chimeric anti-CD20 monoclonal antibodies that deplete CD20+ B cell, has shown to be efficacious in treatment of refractory SLE in case reports including those with transverse myelitis and CNS vasculitis [112, 113]. "
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    • "Since IL-2 receptor (IL-2R) can be up-regulated on activated effector T and B lymphocytes too, the use of CD25 (alpha chain of IL-2R) as a Treg marker has understandably its limitation. Nevertheless, the identification of Foxp3, a relatively more specific if not exclusive marker of Treg, later allowed further verifications for the proposed link between Treg aberrations and systemic autoimmunity [49] [50] [51] [53] [57] [61] [68] [71] [73] [74] [76] [83] [88] [100]. "
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    • "Regulatory T cells (T-reg) are attracting increased attention as a mechanism of immune regulation and suppression of autoimmunity. In lupus, T-regs are often, though not always, found in lower numbers than in controls [26–31]. Those T-regs that are present in lupus are inefficient at suppressing inflammation and T-cell proliferation [27, 29, 30, 32]. "
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