Phatak S, Chaurasia S, Mishra S K, Gupta R, Agrawal V, Aggarwal A, Misra R
Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Clin Exp Immunol. 2017 Mar;187(3):376-382. doi: 10.1111/cei.12894. Epub 2016 Dec 5.
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.
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、维持及浆细胞的存活。狼疮性肾炎（LN）患者的肾脏中已证实存在B细胞浸润。BAFF和APRIL的血清水平与狼疮疾病活动度的关系并不一致。我们评估了尿液中BAFF和APRIL作为LN生物标志物的情况。研究了36例增殖性狼疮性肾炎（AN）患者、10例无肾炎的活动性狼疮（AL）患者和15名健康对照者（HC）。采用酶联免疫吸附测定（ELISA）法检测血清和尿液中的APRIL和BAFF水平。尿液水平根据尿肌酐排泄量进行标准化。尿液水平与传统疾病活动标志物及组织学进行相关性分析。对20例AN患者在接受环磷酰胺治疗6个月后重新评估水平。AN患者尿液中APRIL（uAPRIL）和BAFF（uBAFF）水平显著升高。在AN患者中，uAPRIL与肾脏系统性红斑狼疮疾病活动指数（SLEDAI）呈中度相关（r = 0·36，P < 0·05），而uBAFF则无此相关性。在受试者工作特征曲线（ROC）分析中，uBAFF和uAPRIL在区分肾炎和非肾炎方面的曲线下面积（AUC）分别为0·825和0·781，其表现优于低C3、C4及升高的抗双链DNA抗体。血清水平与uBAFF（r = 0·187，P = 0·261）和uAPRIL（r = 0·114，P = 0·494）无相关性。治疗后uAPRIL水平降低（平均从125 pg/mg降至36 pg/mg，P < 0·05）。16例有反应者的uBAFF水平降低，而4例无反应者中有2例水平升高。因此，uBAFF和uAPRIL是增殖性狼疮性肾炎的潜在生物标志物。
