Research Of Immunopathogenesis In Patients With Systemic Lupus Erythematosus

Objective1. To investigate the changes of regulatory T cells (Treg) and Th17 in patients with new-onset and untreated(without taking corticosteroids at least) systemic lupus erythematosus (SLE). At the same time, the plasma concentrations of interleukin-17 (IL-17), interleukin-23(IL-23), interleukin-6 (IL-6) were detected. To analyze if the changes of Treg, Th17 and cytokines play roles in the pathogenesis of SLE.2. To investigate the relationship between the change of C-reactive protein(CRP) and disease activity, atherosclerotic pathogenesis in patients with new-onset SLE.3. To explore MMPs and TIMPs in the pathogenesis of LN patients.Materials and methods1.58 new-onset, untreated SLE patients and 20 age and sex-matched healthy controls were enrolled in this study.58 SLE patients were divided into two groups based on SLE disease activity index (SLEDAI) score. One group was active and the other was relative inactive (abbreviated "inactive" below). The percentages of CD4+CD25+, CD4+CD25high and Th17 in PBMC were determined by flow cytometry in all subjects. The levels of plasma IL-17, IL-23 and IL-6 were detected by Enzyme-linked immunosorbent assay (ELISA) in all subjects.2. The level of CRP was measured by nephelometry in 58 new-onset, untreated SLE patients and 58 age and sex matched healthy controls; The intima medial thickness(IMT) of common carotid artery was detected by high resolution ultrasonography in all subjects.3.24 SLE patients with LN and 20 SLE patients with non lupus nephritis were enrolled in this study.31 age and sex matched healthy volunteers were also included as controls. The serum levels of MMP-2,9 and TIMP-1,2 of all subjects were measured by ELISA.Results1. CD4+CD25+Treg in PBMC in active group were lower than that of inactive group and healthy control group (P＜0.05 or P<0.01). CD4+CD25high T cells were significant lower in active group than that of healthy control group (P＜0.05). The percentage of Th17 in PBMC in active group and plasma concentrations of IL-6, IL-17, IL-23 were higher than that of inactive group and healthy control group (P<0.05 or P＜0.01). The ratio of CD4+CD25+ to Th17 in active SLE patients was significant lower than that of inactive SLE patients and healthy controls (P<0.01). No differences were observed in the above markers between inactive group and healthy group (P>0.05). Both the ratio of CD4+CD25+ to Thl7 and the levels of IL-6, IL-17, IL-23 correlated with SLEDAI in active SLE patients (P<0.01 or P<0.05).2. Both of the levels of CRP and IMT were higher in active patients than those of inactive patients and healthy controls (P＜0.01 or P<0.05). Both of the levels of CRP and IMT positively correlated with SLEDAI in active patients (both P＜0.01). At the same time, the level of CRP was correlated with the level of IMT positively in active patients (P＜0.01).3. The levels of MMP-2, MMP-9 and the ratio of MMP-9 to TIMP-1 in patients with LN were significantly higher than non-nephritis SLE patients and healthy control subjects (P <0.05 or P< 0.01). The level of TIMP-2 in LN patients was significantly higher than that of healthy control subjects. The level of MMP-2 was significantly higher in non-nephritis SLE patients than that of healthy control subjects (P<0.01). No statistically differences in the levels of MMP-9, TIMP-2 and the ratio of MMP-9 to TIMP-1 between non-nephritis SLE patients and healthy control subjects were observed (P>0.05). The level of TIMP-1 among LN patients, non-nephritis patients and healthy controls was comparable (P>0.05). The ratio of MMP-9 to TIMP-1 in LN patients were significantly correlated with the level of CRP and SLEDAI, whereas, no correlation between this ratio and the concentration of C3 as well as 24 hours urine protein was observed in these LN patients.Conclusion1. CD4+CD25+ and CD4+CD25high T cells were significant lower in new-onset active SLE patients. The percentage of Th17 and the concentration of IL-6, IL-17 and IL-23 were significant higher in new-onset active patients. Moreover, the ratio of CD4+CD25+ to Th17 and the concentrations of IL-6, IL-17, IL-23 were correlated with disease activities. The mechanism maybe the decrease of Treg induced the increase of IL-6, IL-23 and the latter resulting in the elevation of Th17 and IL-17. Then the inflammation was initiated. Th17 as a new identified help T cell correlated closely with the pathogenesis of SLE. Moreover, the changes of Treg and related cytokines contributed to the pathogenesis of SLE.2. There was obvious inflammation in new-onset SLE patients especially in active patients. The level of CRP correlated with the atherosclerotic pathogenesis in SLE patients.3. The imbalance between MMP-9 and TIMP-1 may contribute to the pathogenesis of LN patients. Measurement of MMPs and TIMPs may be helpful in the early identification of lupus patients with LN.