[Immunological characteristics of chronic graft versus host diseases murine model with lupus nephritis].

OBJECTIVE: To establish the murine systemic lupus erythematosus (SLE) model of chronic graft versus host diseases(cGVHD). To analyze the pathological changes and serological and immunological features in the animals. METHODS: Female (C57BL/10 x DBA/2)F1 hybrids aged 6-8 weeks were randomly divided into model group and healthy controls (HC). Lymphocytes from female DBA/2 were injected intravenously to the model group on days 0, 3 and 8, while PBS were injected to the HC under the same condition as a control group. Bradford was applied to monitor the development of albuminuria quantitively. Sera were tested by enzyme linked immunosorbent assay (ELISA) and indirect immunofluorescence (IIF) for the presence of autoantibodies. To compare the differences of CD4+ CD25+ Treg cells between the two groups by flow cytometry (FCM) and the differences in the expression of Foxp3 by real time polymerase chain reaction(RT-PCR). The kidneys of model mice were removed in the 12th week and were made frozen sections for direct immunofluorescence(DIF)and paraffin imbedding for PASM staining. RESULTS: The titers of proteinuria in model group in the 6th week, 8th week, 10th week, and 12th week were significantly higher than those of the HC groups(P=0.004, 0.005,respectively). The titers of anti-dsDNA and anti-nucleosome antibodies were significantly increased in the model group compared with the HC (P<0.05). And the positive rates curves of ANA, anti-dsDNA Abs and anti-nucleosome Abs in model group were significantly different from those of control group (P<0.05). And The proportions of CD4+CD25+ regulatory T cells from peripheral blood of model group were significantly lower than those of control group (P=0.002), while the expression of Foxp3, one of the most important biomarkers of Treg cells, was not significant. There were mesangial matrix expansion and mesangial cell proliferation in the nephritic pathology in model group and the depositions of IgG along the glomerular capillary walls and in the mesangium were observed in model group. There were no pathological changes and depositions in HC group. CONCLUSION: It has been proved that there are not only protienuria and autoantibodies, but also decrease of the regulatory T lymphocytes in murine model of cGVHD. All of these results suggest that the cGVHD murine SLE models were successfully established.

[Related factors of systemic lupus erythematosus: clinical analysis of 203 cases].

OBJECTIVE: To investigate the related factors of systemic lupus erythematosus (SLE) and the situation of diagnosis and treatment after onset. METHODS: 203 SLE patients, 11 males and 192 females, with a male/female ratio of 1:17, average onset age of (32 +/- 14), and average course of 3 years, were followed up and the related factors such as risk factors, family history and the situation of diagnosis and treatment were studied. RESULTS: 63 patients (31%) had the history of overworking before falling ill; 47 patients (23.2%) had suffered from infection before SLE onset. Other risk factors, such as solarization, emotional fluctuation, menstrual disorder, abortion, dyeing, and chemical drug contacting accounted for 14.3%, 14.3%, 9.4%, 6.9% , 4.9%, and 1.5% respectively. 16 patients (7.9%) had positive family history. 120 patients got the correct diagnosis at the first visit. 83 patients had been misdiagnosed for less than 1 year to 14 years. 47 of the 83 patients (23.2%) failed to get the correct diagnosis for more than one year. 140 of the 203 patients (69.0%) were given glucocorticoid and/or immunosuppressant as the first choice treatment measures after the diagnosis was confirmed. 39 of the 203 patients (19.2%) chose traditional Chinese medicine or folk prescription as the first choice. And 24 of the 203 patients (11.8%) used anti-inflammatory, and antipyretic drugs. 128 patients (63.1%) failed to continue to work. CONCLUSION: Overworking, infection, solarization, and emotional fluctuation may be related to the onset of SLE. A great part of SLE patients can not be diagnosed early and treated promptly. SLE brings bad influence on the life quality of patients.

Toll-like receptor 9 is correlated to disease activity in Chinese systemic lupus erythematosus population.

BACKGROUND: Toll like receptor (TLR) 9 has been shown to play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE) in animal models. Its pathogenic role in human SLE, however, was poorly elucidated. This study was performed to investigate the role of TLR9 involved in the aberrant signaling pathway and its correlation with disease activity in SLE. METHODS: mRNA level of TLR9 and interferon (IFN) regulatory factor 5 (IRF5) in peripheral blood mononuclear cells (PBMCs) were determined by real-time polymerase chain reaction (PCR). IFN-a expression was measured in the serum of the SLE patients by enzyme-linked immunosorbent assay (ELISA). RESULTS: TLR9 expression was significantly higher in SLE patients than that in health controls (P = 0.011). SLE patients with positive anti-dsDNA antibody had significantly higher expression of TLR9 than that with negative anti-dsDNA antibody (P = 0.001). TLR9 expression was positively correlated with fever (P = 0.017), alopecia (P = 0.046), safety of estrogens in lupus erythematosus national assessment SLE disease activity index (SELENA-SLEDAI) score (r(s) = 0.385, P = 0.003), and the level of IRF5 (r(s) = 0.35, P = 0.027) and IFN-a (r(s) = 0.627, P = 0.001) in SLE patients. CONCLUSION: TLR9 is associated with SLE disease activity and might be involved in the IFN-a pathway of SLE.