Association Study Of Intracellular ROS Levels Change On T/B Cell And SLE Patients

Background Systemic lupus erythematosus(SLE) is a typical autoimmune connective tissue disease characterized by a multitude of auto-antibody production, complement activation and immune-complex deposition, which leads to enhanced innate immune responses in affected tissues. SLE has a tendency to gender and age, which predominantly affects women(at a 9:1 ratio). To date, the etiology and pathogenetic mechanisms responsible for SLE occurrence have not been clearly elucidated. In SLE, the state of self-tolerance of T/B cells and other immune cells are destroyed and produce a large number of auto-antibodies resulting in tissue injury and organ damage. So to understand the mechanism of self-tolerance destruction and auto-antibodies formation in SLE has become a focus of the disease research. The imbalance reduction-oxidation(redox) system delayed the clearance of apoptotic cells which may provide unremitted interactions between reactive oxygen species(ROS) and apoptotic cells macromolecules generating neo-epitopes which subsequently induce autoantibody formation, and also is the main cause of humoral immunity and cellular immune disorders. Therefore, compare ROS expression level changes in T/B cells on SLE and normal controls to further expound the pathogenesis of SLE has an important significance.Objective Expression levels of ROS in the T/B cells was compared between the SLE patients and normal controls. Further analyze the relationships between the expressions of ROS in the T/B cells and primary clinical manifestations(like lupus nephritis), clinical laboratory data(like Anyi-RNP), and SLE disease activity. Oxidative burst in B-and T-lymphocytes from SLE patients and healthy controls were investigated in order to gain an insight into the pathogenesis and treatment of SLE.Methods Fifty-seven patients with SLE and thirty normal healthy volunteers which matched to sex and age are recruited at the Department of Rheumatology of Anhui Provincial Hospital and First Affiliated Hospital of Anhui Medical University. Questionnaire was designed according to the SLE disease activity index(SLEDAI) and classification criteria. Demographic data, clinical data, and laboratory data were collected from self-designed questionnaire or by hospital records and reviewed by experienced physicians. Peripheral blood mononuclear cell(PBMCs) used in all experiments were isolated from 5ml of heparinized blood using a Ficoll-Paque Plus density gradient for determining ROS production. The FCM system(FITC,PE,APC)was used to detect the expressions of ROS in T/B cells. All experience data were analyzed by SPSS 10.01 software.Results The mean fluorescence intensity(MFI) of ROS in T cells of SLE patients was more than normal controls, and the difference was statistically significant(Z=-5.02,P<0.001). On the other hand, the MFI of ROS in B cells on SLE patients were decreased(Z=-3.18,P=0.001). In addition, ROS production was significantly higher in T lymphocytes of SLE patients with nephritis as compared to normal controls(P=0.044). However, the ROS level in T or B lymphocytes between less active SLE and more active SLE has no significant difference. Associations of ROS levels with major clinical indicators and laboratory indexes of SLE patients were also analyzed, and the results indicated that the high ROS production in T cells was associated with the presence of proteinuria. Besides this, two clinical and laboratory parameters of SLE, antinuclear(P=0.017) and anti-RNP(P=0.021), both of which were significantly associated with lower ROS level in B lymphocytes. However, SLE patients with positive anti-ds DNA antibodies compared with negative anti-ds DNA antibody, patients with abnormal Sm antibodies with non-Sm antibodies abnormalities, patients with anti-SSA increased with no anti-SSA increased, statistically significant differences of ROS levels in peripheral blood T / B cell have not been found among these groups(all P >0.05).Conclusions In conclusion, the findings of our study suggested increased ROS generation by SLE T- lymphocyte and decreased ROS levels in SLE B- lymphocyte. The above results are intriguing and may indicate some links between B-and T-lymphocytes oxidative activity and the pathogenesis of SLE. This observation warrants further studies will be needed to explore the role of ROS in chronic inflammation and the development and treatment of SLE.