Association between T lymphocyte sub-sets apoptosis and peripheral blood mononuclear cells oxidative stress in systemic lupus erythematosus

Department of Biochemistry, Basic Medical Science Block, Panjab University, Chandigarh, India.
Free Radical Research (Impact Factor: 2.98). 02/2011; 45(5):559-67. DOI: 10.3109/10715762.2011.555765
Source: PubMed

ABSTRACT Increased oxidative stress and lymphocyte apoptosis are a hallmark of the autoimmune disease systemic lupus erythematosus (SLE). However, the association between oxidative stress and T lymphocytes apoptosis has still to be elucidated in SLE. In order to appraise the interaction between oxidative stress and T lymphocyte apoptosis with the severity of disease, oxidative stress profile and T lymphocytes apoptosis were studied. Increased levels of ROS, MDA and CD4(+) lymphocyte apoptosis were positively associated with disease activity while decreased levels of GSH and percentage expression of CD4(+) lymphocyte were negatively associated with disease activity. The decrease in intracellular levels of GSH was negatively associated with T lymphocyte, CD4(+) lymphocyte, CD8(+) lymphocyte apoptosis and intracellular caspase-3 expression. The present study suggests that increased T lymphocyte sub-sets apoptosis may be mediated by decreased intracellular glutathione concentration and severity of disease might be enhanced together by over-production of ROS in SLE.

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    • "The etiology of the disease remains unclear; however, it is thought to be triggered by autoantigens that induce autoantibody production. Apoptotic lymphocytes may be one source of autoantigens, and increased numbers of apoptotic lymphocytes have been reported in SLE (Shah et al., 2011). Notably, apoptotic CD4 + , but not CD8 + , T lymphocytes were found to constitute the main source for the activated lymphocyte derived DNA and other apoptotic cellular constituents that function as autoantigens to induce production of anti-double-stranded DNA (anti-dsDNA) antibodies in SLE (Wen et al., 2012). "
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    ABSTRACT: Emerging data have implicated a critical role for CD4 in the pathogenesis of systemic lupus erythematosus (SLE). This study was designed to delineate the contribution of CD4 + T cells in the pathogenesis of SLE disease. Forty-four patients (3 male: 41 female) and 20 healthy volunteers (4 male: 16 female) were included in the study. CD4 + lymphocytes analysis was done using three-color flow cytometry with antibodies against human-CD95, a prototype cell death receptor, and the chemokine receptor-7 (CCR7) after gating for lymphocytes based on the forward and side scatter. Serum levels of IL-6, IL-12, IL-17, TNF-a and IL-10 cytokines were assayed using ELISA. Disease activity was assessed using the SLE disease activity index (SLEDAI). Based on the expression of CCR7 and CD95, CD4 + lymphocytes were subdivided into three particular subsets; CD4 + CD95 + CCR7 + cells, CD4 + CD95 À CCR7 + cells and CD4 + CD95 + CCR7 À cells. Percentage of CD4 + CD95 + CCR7 + cell subset was significantly higher in patients with SLE with Please cite this article in press as: Aldahlawi, A.M. et al., Analysis of CD95 and CCR7 expression on circulating CD4 + lymphocytes revealed disparate immunoreg-ulatory potentials in systemic lupus erythematosus. Saudi Journal of Biological Sciences (2015), active disease (SLEDAI > 6) and inactive (SLEDAI < 6) as compared with controls (P = 0.005), and it showed a significant positive correlation with ANA titer (P = 0.01), and a negative correlation with WBCs count (P = 0.001). CD4 + CD95 + CCR7 À cell subset was significantly higher in active SLE patients in comparison to patients with inactive disease and controls (P = 0.05, P = 0.005 respectively), and it correlates positively with SLEDAI, IL-6 and IL-17 levels (P = 0.001, 0.05, 0.01 respectively), and negatively with blood WBCs counts (P = 0.001). The third CD4 + CD95 À CCR7 + cell subset was found significantly lower in SLE patients compared with controls , and it was found negatively correlated with IL-10, IL-6, and IL-17. The results show that CD4 + CD95 + subset lacking expression of CCR7 is associated with cell mediated inflammatory response as manifested by its correlation with signs of inflammation, inflammatory cytokines and disease activity index. Whereas, CD4 + CD95 + CCR7 + correlate more with antibody immune responses as manifested by association with serum ANA. These data suggest disparate roles of these cell subsets in the pathophysiology of SLE. A better understanding of the characteristics of CD4 cell subsets may shed light on the pathogenesis of autoimmune diseases, particularly SLE. ª 2015 Production and hosting by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (
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    • "An association between disease activity and ROS production could not be excluded based on the available data. The literature is not concurrent regarding ROS production by SLE-PMN [23,28,29]. For example, Perazzio et al. have shown that neutrophils from SLE patients have an increased capacity to produce ROS, and they did not find any correlation with organ damage or disease activity [23]. "
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    ABSTRACT: Polymorphonuclear leukocytes (PMN) are main effector cells in the acute immune response. While the specific role of PMN in systemic lupus erythematosus (SLE) and autoimmunity is still unclear, their importance in chronic inflammation is gaining more attention. Here we investigate aspects of function, bone marrow release and activation of PMN in patients with SLE. The following PMN functions and subsets were evaluated using flow cytometry; (a) production of reactive oxygen species (ROS) after ex vivo stimulation with phorbol 12-myristate 13-acetate (PMA) or Escherichia coli (E. coli); (b) capacity to phagocytose antibody-coated necrotic cell material; (c) PMN recently released from bone marrow, defined as percentage of CD10−D16low in peripheral blood, and (d) PMN activation markers; CD11b, CD62L and C5aR. SLE patients (n = 92) showed lower ROS production compared with healthy controls (n = 38) after activation ex vivo. The ROS production was not associated with corticosteroid dose or other immunotherapies. PMA induced ROS production was significantly reduced in patients with severe disease. In contrast, neither ROS levels after E. coli activation, nor the capacity to phagocytose were associated with disease severity. This suggests that decreased ROS production after PMA activation is a sign of changed PMN behaviour rather than generally impaired functions. The CD10−CD16low phenotype constitute 2% of PMN in peripheral blood of SLE patients compared with 6.4% in controls, indicating a decreased release of PMN from the bone marrow in SLE. A decreased expression of C5aR on PMN was observed in SLE patients, pointing towards in vivo activation. Our results indicate that PMN from SLE patients have altered function, are partly activated and are released abnormally from bone marrow. The association between low ROS formation in PMN and disease severity is consistent with findings in other autoimmune diseases and might be considered as a risk factor.
    Arthritis Research & Therapy 06/2014; 16(3):R120. DOI:10.1186/ar4575 · 3.75 Impact Factor
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    • "SOD1 and SOD3 contain copper and zinc, while SOD2 has manganese in its reactive center. Several groups have reported a decreased activity of SOD and formation of auto-antibody against SOD enzyme in SLE patients [14,21,30]. It is speculated that the antibody to SOD is responsible for inactivation of enzyme and exaggerated oxidative damage in SLE. "
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    ABSTRACT: Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease whose etiology remains largely unknown. The uncontrolled oxidative stress in SLE contributes to functional oxidative modifications of cellular protein, lipid and DNA and consequences of oxidative modification play a crucial role in immunomodulation and trigger autoimmunity. Measurements of oxidative modified protein, lipid and DNA in biological samples from SLE patients may assist in the elucidation of the pathophysiological mechanisms of the oxidative stress-related damage, the prediction of disease prognosis and the selection of adequate treatment in the early stage of disease. Application of these biomarkers in disease may indicate the early effectiveness of the therapy. This review is intended to provide an overview of various reactive oxygen species (ROS) formed during the state of disease and their biomarkers linking with disease. The first part of the review presents biochemistry and pathophysiology of ROS and antioxidant system in disease. The second part of the review discusses the recent development of oxidative stress biomarkers that relates pathogenesis in SLE patients and animal model. Finally, this review also describes the reported clinical trials of antioxidant in the disease that have evaluated the efficacy of antioxidant in the management of disease with ongoing conventional therapy.
    Journal of Biomedical Science 03/2014; 21(1):23. DOI:10.1186/1423-0127-21-23 · 2.76 Impact Factor
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