尿B细胞活化因子(BAFF)和增殖诱导配体(APRIL):活动性狼疮性肾炎的潜在生物标志物

S. Phatak, S. Chaurasia, S. Mishra, R. Gupta, V. Agrawal, A. Aggarwal, R. Misra
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引用次数: 31

摘要

B细胞活化因子(BAFF)和增殖诱导配体(APRIL)有助于B细胞的活化、维持和浆细胞的存活。狼疮性肾炎(LN)患者肾脏中已发现B细胞浸润。血清BAFF和APRIL水平与狼疮疾病活动的关系不一致。我们评估了尿液BAFF和APRIL水平作为LN的生物标志物。本文对36例增殖性狼疮肾炎(AN)患者、10例活动性狼疮无肾炎(AL)患者和15例健康对照(HC)患者进行了研究。采用酶联免疫吸附试验(ELISA)测定血清和尿液中的APRIL和BAFF水平。尿肌酐排泄水平正常。尿水平与常规疾病活动标志物和组织学相关。在环磷酰胺治疗6个月后,对20例AN患者的水平进行重新评估。尿APRIL (uAPRIL)和BAFF (uBAFF)水平在AN组显著升高。uAPRIL与肾脏系统性红斑狼疮疾病活动指数(SLEDAI)中度相关(r = 0.36, P < 0.05),而uBAFF与肾系统性红斑狼疮疾病活动指数(SLEDAI)不相关。在受试者操作曲线(ROC)分析中,uBAFF和u四月在鉴别肾炎和非肾炎的曲线下面积(AUC)分别为0.825和0.781,优于低C3、C4和高抗dsDNA抗体。血清水平与uBAFF (r = 0.187, P = 0.261)、uAPRIL (r = 0.114, P = 0.494)无相关性。治疗后uAPRIL水平降低(平均125 pg/mg至36 pg/mg, P < 0.05)。16名应答者的uBAFF水平降低,而4名无应答者中的2名水平升高。因此,uBAFF和uAPRIL是增殖性狼疮性肾炎的潜在生物标志物。
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Urinary B cell activating factor (BAFF) and a proliferation‐inducing ligand (APRIL): potential biomarkers of active lupus nephritis
B cell activating factor (BAFF) and a proliferation‐inducing ligand (APRIL) help in B cell activation, maintenance and plasma cell survival. B cell infiltration has been demonstrated in kidneys of patients with lupus nephritis (LN). Serum levels of BAFF and APRIL have shown inconsistent relationships with lupus disease activity. We evaluated urinary levels of BAFF and APRIL as biomarker for LN. Thirty‐six patients with proliferative lupus nephritis (AN), 10 with active lupus without nephritis (AL) and 15 healthy controls (HC) were studied. APRIL and BAFF levels were measured in both serum and urine using enzyme‐linked immunosorbent assay (ELISA). Urine levels were normalized for urinary creatinine excretion. Urine levels were correlated with conventional disease activity markers and histology. Levels were reassessed in 20 AN patients at 6 months after treatment with cyclophosphamide. Urinary APRIL (uAPRIL) and BAFF (uBAFF) levels were raised significantly in AN. uAPRIL, but not uBAFF, correlated moderately with renal Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in AN (r = 0·36, P < 0·05). On receiver operator curve (ROC) analysis, uBAFF and uAPRIL showed an area under the curve (AUC) of 0·825 and 0·781, respectively, in differentiating between nephritis and non‐nephritis, which performed better than low C3, C4 and raised anti‐dsDNA antibodies. There was no correlation of serum levels with uBAFF (r = 0·187, P = 0·261) and uAPRIL (r = 0·114, P = 0·494). uAPRIL levels reduced after treatment (mean 125 pg/mg to 36 pg/mg, P < 0·05). uBAFF levels reduced in 16 responders while two of four non‐responders had increase in levels. Thus, uBAFF and uAPRIL are potential biomarkers of proliferative lupus nephritis.
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