Clinical And Experimental Study Of Vincristine And Small Doses Of Cyclophosphamide On Patients With Systemic Lupus Erythematosus

BackgroundsSystemic lupus erythematosus (SLE) is a diffuse connective tissue disease characterized by autoimmune involved autoimmune inflammation. SLE has long course and high mortality. At present, although we can not effect a radical cure of it, reasonable treatment of SLE can relieve the illness for most of the patients completely. Drawing on the experience of combination chemotherapy in lymphoma, and according to cell kinetics theory, we choose vincristine (VCR), the specificity cell cycle drug and small doses of cyclophosphamide (CTX), the nonspecific cell cycle drug to treat SLE. And we have confirmed that combination therapy was effective and safe through clinical and rat model for lupus research.There is immune dysfunction through its whole pathogenic process. In recent years, the study of Th17and Treg cells has been paid great attention to.The percentage of Th17cells was higher in peripheral lymphocyte in SLE, and the percentage of Treg cells was lower in peripheral lymphocyte in SLE. It showed that Th17and Treg cells played a part in pathogenic process of SLE.We set up the study to evaluate efficacy and safety of VCR combined with small doses of CTX and to investigate their influences on the Th17and Treg cells, and then to provide more powerful scientific basis for clinical combination therapy henceforth.Objectives1. To evaluate the efficacy of VCR combined with low doses of CTX therapy.2. To evaluate the safety of VCR combined with low doses of CTX therapy.3. To investigate the levels of the percents of Th17cells and Treg cells in SLE patients. And to investigate the change of Th17cells and Treg cells between pre and post treatment.Methods1. Part of clinical:We have carried out two centers, randomized, controlled and single blind clinical research for24weeks.36cases of active SLE patients who included in the study were divided into VCR combined with low doses of CTX group, single with high doses of CTX group, and VCR combined with high doses of CTX group randomly. There were three time points included the baseline, week12and week24. To study the change of SLEDAI, C3, ESR, ALB, Cr.2. Part of experiment:We have detected the percentage of Th17cells and Treg cells for36actively patients with SLE and10normal people. To detect the change of Th17cells and Treg cells. There were three research points included the baseline, week12and week24. Results1. Evaluation of effic acy:At the baseline, SLEDAI, ESR, C3, ALB and Cr were no statistically significant differences during the three groups.At week12and24, SLEDAI, ESR, Cr decreased significantly in the three groups compared with the baseline, while C3and ALB increased significantly. But there were no statistically significant differences during the three groups.Compared to week12, SLEDAI and ESR at week24decreased greatly in three groups, inversely C3and ALB increased significantly. There were no statistically significant differences during the three groups. But Cr didn’t change significantly in single with high doses of CTX group compared to VCR combined with low doses of CTX group and VCR combined with high doses of CTX group.2. Evaluation of safety:There was no difference of adverse effect during the three groups. Even there were fewer patients who had menstrual disorders and leukopenia in VCR combined with low doses of CTX group.3. The change of Th17and Treg cells:At the baseline, compared to normal people, the percentage of Th17cells increased significantly and the percentage of Treg cells decreased significantly. But there were no statistically significant differences during the three groups.At week12and24, the percentage of Th17cells decreased greatly in the three groups compared to the baseline, while the percentage of Treg cells increased significantly. But there were no statistically significant differences during the three groups. Compared to week12, the percentage of Th17cells at week24decreased significantly in the three groups, and the percentage of Treg cells at week24increased significantly. There were no statistically significant differences during the three groups.Conclusions1. VCR combined with low doses of CTX can improve SLE patients’ conditions remarkably, and so can the other two groups.2. The adverse effect of VCR combined with low doses of CTX was lower than the other two groups.3. The percentage of Th17cells increased and the percentage of Treg cells decreased in SLE patients. And the percentage of Th17cells increased greatly and the percentage of Treg cells decreased significantly in VCR combined with low doses of CTX group, as well as in the other two groups. 4. Combined low dose cyclophosphamide treatment group can significantly receded the level of BAFF and BAFF-RmRNA.