| Systemic lupus erythematosis (SLE) is a severe autoimmune disease with multiorgan and multisystem lesioned, characterized by production of various antinuclear antibodies (ANA), including anti-dsDNA, anti-Sm, anti-RNP antibody, et al. The spontaneous occurrence of antibodies against the dsDNA is a highly specific marker for the diagnosis of SLE and proved to be pathogenetic. There are many different opinions about the mechanisms of tolerance-broken. Once we extracted and purified chromatin and DNA from unactivated lymphocytes and activated lymphocytes respectively, immunized syngeneic mice separately. We found that chromatin and DNA from activated lymphocytes induced many kinds of ANA, such as anti-dsDNA, anti-histone antibodies, while none of the mice immunized by chromatin and DNA of unactivated lymphocytes produced autoantibodies. It indicated that DNA derived from activated lymphocytes (ALD-DNA), which changed its immunogenicity, was one of the important initiators to trigger the production of ANA. Since the extensive lymphocytes activation and excessive apoptosis could be observed in the SLE patients, the large amount of released DNA may comprise the major source of such kind of autoantigen to induced the production of autoantibodies.As one of the normal glycoprotein in the serum, Serum amyloid P component (SAP) was found to have the capacity of binding DNA, chromatin and nucleosome specifically and calcium-dependently under the physiological conditions, and the SAP gene knock-out mice could produce ANAs spontaneously and suffered from severe glomerulonephritis, just resembled the SLE syndrome. We postulated that SAP interplayed with the nuclear antigen released from apoptotic cells and was involved in the disposal of the DNA and chromatin, which would inhibit the induction of autoantibody. In this article we try to analyse the relationship between SAP and SLE, then purify theSAP protein and study its role in the process of the DNA clearance and its effect on the induction of anti-dsDNA antibody in vivo and in vitro, further observe the possibility of the inhibition of SLE-like syndrome based on the gene injection of SAP. This research may provide experimental and theoretic basis for the new prevention strategy of SLE.PART I Research on the correlation between SAP level and systemic lupus erythematosus (SLE)In order to analyse the relationship between SAP and SLE, we detected the serum SAP levels of the patients and normal controls by ELISA firstly, it showed that the SAP concentration of SLE patients was (50.35(22.16(g/ml), which was much higher than that of the normal controls (32.78(23.48(g/ml), there was significantly statistic difference between them (P<0.01). Then we detected the concentration of DNA in both serum by DNA-EB fluorescent assay, it showed that the DNA level of SLE patients was (76.54(14.40(g/ml), which was much higher than that of the normal controls (36.91(14.40(g/ml), there was significantly statistic difference between them (P<0.01). Pearson correlation analysis showed that SAP concentration correlated positively with DNA level (R=0.5014,P<0.01). Subsequently we compared the DNA and SAP level between the patients in active and inactive phase, it showed that both the SAP and DNA concentrations of the patients in active phase increased significantly than those of the patients in inactive phase (P<0.01). The SAP/DNA ratios decreased obviously in SLE patients compared to the normal persons (P<0.01), which suggested that the SAP level were relatively insufficient in SLE patients. We also found that the SAP/DNA ratios were negative-correlation with the anti-dsDNA antibodies level(r=-0.541,P<0.05), what mentioned above suggested that SAP plays certain role in the etiology of SLE. PATR II The in vitro study on the binding characteristics of SAP to DNA and the later events1. Purification of murine SAPWe induced the acute phase response of BALB/c mice by injection of LPS through peritoneal, then collected the serum after 24 hours, the SAP protein w...
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