中性粒细胞细胞外网络与B淋巴细胞在狼疮肾炎患者肾组织的表达及其意义

目的 探讨中性粒细胞细胞外网络(NET)在狼疮肾炎(LN)患者肾组织中的表达与狼疮活动的关系.方法 采用免疫组织化学技术,分别检测NET(以瓜氨酸化的组蛋白H3为标志)在20例LN、8例微小病变(MCD)患者和3例健康对照的肾组织的表达,同时检测相应部位B淋巴细胞(CD19标志)的浸润.分析LN患者肾组织活动指数和慢性指数评分,以及它们与NET的关系.结果 LN患者肾小球中NET表达显著高于健康对照组和MCD组(1.056±0.985比0±0、0±0,均P＜0.01).在中、重度增生的系膜细胞、细胞新月体、有炎性细胞浸润的肾小管间质,NET表达显著上调；系膜细胞中、重度增生肾小球的NET表达显著高于其他类型肾小球,差异均有统计学意义(均P＜0.01).中、重度系膜细胞增生肾小球的平均NET阳性细胞数与LN病理活性指数呈正相关(r=0.620,P=0.004)；与SLE-DAI评分呈正相关(r=0.492,P=0.027)；与肾小管中NET阳性细胞数呈正相关(r=0.558,P=0.011).肾间质NET阳性细胞数与肾间质阳性B淋巴细胞数呈正相关(r=0.573,P=0.008);与LN病理慢性指数呈正相关(r=0.645,P=0.002).结论 NET在LN患者肾组织广泛表达,肾小球中浸润的NET可能参与了LN患者肾组织的活动性损伤.

Expression of neutrophil extracellular trap and B lymphocyte in renal tissue of patients with lupus nephritis and its significance

Objective To investigate the association of expressions of neutrophil extracellular trap (NET) and B lymphocyte in renal tissue with lupus activity in patients with lupus nephritis (LN). Methods Immunohistochemistry was used to detect the expression of NET (citrullinated histone H3 as the marker) and the infiltration of B lymphocyte (CD19 as the marker) in renal specimens of three groups [LN group, n=20; minimal change disease (MCD) group, n=8; healthy control group, n=3]. The chronic index and SLE-disease activity index (SLE-DAI) in renal tissues of LN and their correlations with NET and B lymphocytes were examined. Results The expression of NET was not found in the renal tissues of healthy control group and MCD group, while it increased significantly in LN group, especially in glomeruli with moderate and severe mesangial cells proliferation, cellular crescents, and tubulointerstitium with inflammatory cell infiltration. Compared with other types of glomeruli, the expression of NET was significantly up-regulated in glomeruli with moderate and severe mesangial cell proliferation(P<0.01). In the glomeruli with moderate and severe glomerular mesangial cell proliferation, the mean number of NET positive cells was positively correlated with renal pathological active index (r=0.620, P=0.004), the score of SLE-DAI (r=0.492, P=0.027) and the mean number of NET positive tubular cells (r=0.558, P=0.011). In renal interstitium, the NET positive cells were positively correlated with CD19 positive B lymphocytes (r=0.573, P=0.008) and renal pathological chronic index(r=0.645, P=0.002). Conclusion NET is widely expressed in the renal tissues of lupus nephritis, which may play a role in the active damage of glomeruli.