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
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.
Available from: PubMed Central
- "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 . 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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ABSTRACT: Neuropsychiatric systemic lupus erythematosus (NPSLE) is the least understood, yet perhaps the most prevalent manifestation of lupus. The pathogenesis of NPSLE is multifactorial and involves various inflammatory cytokines, autoantibodies, and immune complexes resulting in vasculopathic, cytotoxic and autoantibody-mediated neuronal injury. The management of NPSLE is multimodal and has not been subjected to rigorous study. Different treatment regimens include nonsteroidal anti-inflammatory drugs, anticoagulation, and immunosuppressives such as cyclophosphamide, azathioprine, mycophenolate mofetil, and methotrexate. For refractory NPSLE, intravenous immunoglobulin (IVIG), plasmapheresis, and rituximab have been used. Adjunctive symptomatic treatment complements these therapies by targeting mood disorders, psychosis, cognitive impairment, seizures or headaches. Several new biological agents are being tested including Belimumab, a human monoclonal antibody that targets B lymphocyte stimulator. This review focuses on the pathophysiology, treatment, and new potential therapies for neuropsychiatric manifestations of systemic lupus erythematosus.
Available from: Susanne Sattler
- "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              . "
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ABSTRACT: Systemic lupus erythematosus (SLE), formerly named ‘disseminated lupus erythematosus’, is an organ-non-specific autoimmune disease that has a largely unknown aetiology. Multiple susceptibility genes as well as environmental factors are found to be involved in the lupus pathogenesis (multi-factorial) [1, 2]. Also known as the prototype of autoimmune diseases, lupus is very intriguing both clinically and immunologically for its systemic nature and complexity in pathogenesis. The disease is characterized by multi-organ involvement and presence of autoantibodies to a variety of self antigens, particularly of the nuclear components . Deposition of the immune complexes may trigger complement activation causing tissue damages. The broad auto-reactivities and hyperactivity of B cells are known to be predominately T cell-dependent , but the cellular and molecular mechanisms underlying such a systemic loss of B and T cell tolerance are yet to be fully understood. In contrast to B cell hyperactivity , reduced Interleukin 2 (IL-2) production and aberrant responsiveness of T cells are characteristic of SLE [6, 7]. Moreover, impaired cellular immunity, complement deficiency, defects in the clearance of dying cells by macrophages [8-10], roles of DC and the disrupted mechanisms of tolerance induction [11-14] are among many immunological characteristics of, or potential mechanisms proposed for, the disease.
Available from: Daniel N Clark
- "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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ABSTRACT: The pleiotropic cytokine interferon alpha is involved in multiple aspects of lupus etiology and pathogenesis. Interferon alpha is important under normal circumstances for antiviral responses and immune activation. However, heightened levels of serum interferon alpha and expression of interferon response genes are common in lupus patients. Lupus-associated autoantibodies can drive the production of interferon alpha and heightened levels of interferon interfere with immune regulation. Several genes in the pathways leading to interferon production or signaling are associated with risk for lupus. Clinical and cellular manifestations of excess interferon alpha in lupus combined with the genetic risk factors associated with interferon make this cytokine a rare bridge between genetic risk and phenotypic effects. Interferon alpha influences the clinical picture of lupus and may represent a therapeutic target. This paper provides an overview of the cellular, genetic, and clinical aspects of interferon alpha in lupus.
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