摘要
目的探讨系统性红斑狼疮(SLE)患者血清IL-21对正常B细胞分泌功能和凋亡的影响。方法收集初发未经治疗的活动期SLE患者和健康对照者血清各20例,磁珠分选健康对照者外周血CD19+B细胞,与SLE患者、健康对照者血清和/或重组IL-21受体融合蛋白共培养,5 d后收集上清及细胞,免疫比浊法测上清IgG、IgM水平,ELISA法测上清抗双链DNA抗体,膜连蛋白Ⅴ/碘化丙啶法检测B细胞凋亡率。结果(1)正常B细胞+SLE患者血清组IgG、IgM及抗双链DNA抗体水平高于SLE患者血清+培养基组[(5.84±1.79) g/L比(4.25±1.48) g/L,P=0.000;(0.46±0.21) g/L比(0.43±0.21) g/L,P=0.003;(127.76±70.24) IU/ml比(115.15±63.88) IU/ml,P=0.014];而正常B细胞+健康对照者血清组IgG、IgM及抗双链DNA抗体水平无明显改变(P值均〉0.05);(2)加入重组IL-21受体融合蛋白后,正常B细胞+SLE患者血清+重组IL-21受体融合蛋白组IgG、IgM及抗双链DNA抗体水平减少[(5.26±1.62) g/L比(5.84±1.79 ) g/L,P=0.006;(0.42±0.20) g/L比(0.46±0.21) g/L,P=0.002;(118.00±69.62) IU/ml比(127.76±70.24) IU/ml,P=0.012];(3)正常B细胞+SLE患者血清组B细胞凋亡率高于正常B细胞+健康对照者血清组[(47.88±12.65)%比(38.86±10.32)%,P=0.004];加入重组IL-21受体融合蛋白后,正常B细胞+SLE患者血清+重组IL-21受体融合蛋白组B细胞凋亡率下降[(42.08±12.52)%比(47.88±12.65)%,P=0.001]。结论IL-21可诱导正常B细胞分化为免疫球蛋白分泌细胞分泌抗体,同时诱导正常B细胞凋亡,阻断IL-21可能成为治疗SLE的新方法。
ObjectiveTo investigate the secretory capacity and apoptosis of interleukin (IL)-21 induced normal B cells by co-culture with serum from patients with systemic lupus erythematosus (SLE).MethodsSerum from twenty new-onset SLE patients and 20 healthy donors were collected. CD19+ B cells from the normal controls were co-cultured with serum from SLE patients in the presence or absence of IL-21-R-FC(4 μg/ml). Supernatant IgG and IgM concentration were measured by immunoturbidimetric assay on day 5. Supernatant anti-dsDNA level was determined by ELISA. The percentage of apoptotic cells was detected by flow cytometer.ResultsIgG, IgM and anti-dsDNA levels in normal B cells with SLE serum were significantly higher than those in the serum of SLE patients alone [(5.84±1.79)g/L vs (4.25±1.48)g/L, P=0.000; (0.46±0.21)g/L vs (0.43±0.21)g/L, P=0.003; (127.76±70.24)IU/ml vs (115.15±63.88) IU/ml, P=0.014 respectively]. However, no significant differences were found in the group of normal B cells with non-homologous serum from normal controls (P〉0.05). Supernatant IgG, IgM and anti-dsDNA levels in normal B cells with SLE serum significantly decreased while IL-21R-fusion protein was added [(5.26±1.62)g/L vs (5.84±1.79)g/L, P=0.006; (0.42±0.20)g/L vs (0.46±0.21)g/L, P=0.002; (118.00±69.62)IU/ml vs (127.76±70.24)IU/ml, P=0.012 respectively]. The apoptotic rate of B cells with SLE serum was significantly higher than that with normal serum [(47.88±12.65)% vs (38.86±10.32)%, P=0.004]. But adding IL-21R-fusion conversed the apoptotic rates [(42.08±12.52)% vs (47.88±12.65)%, P=0.001].ConclusionsSLE serum could induce normal B cells to form immunoglobulin secreting cells and producing autoantibodies, or apoptosis in pathological conditions. IL-21 might be considered as a potential therapeutic target of SLE.
出处
《中华内科杂志》
CAS
CSCD
北大核心
2017年第2期116-120,共5页
Chinese Journal of Internal Medicine
基金
国家自然科学基金(30872333、81072404)
广西医科大学青年科学资助基金(GXMUYSF201335)
广西高等学校科学研究项目(KY2015LX062)