Jourde-Chiche Noémie, Whalen Elizabeth, Gondouin Bertrand, Speake Cate, Gersuk Vivian, Dussol Bertrand, Burtey Stephane, Pascual Virginia, Chaussabel Damien, Chiche Laurent
Department of Nephrology, Aix-Marseille University, AP-HM, Hôpital Conception, UMR_S 1076, Vascular Research Center of Marseille, Marseille, France.
Systems Immunology Department, Benaroya Research Institute, Seattle.
Rheumatology (Oxford). 2017 Mar 1;56(3):477-487. doi: 10.1093/rheumatology/kew439.
LN is a severe complication of SLE. Non-invasive biomarkers are needed for identifying patients at risk of a renal flare, for differentiating proliferative from non-proliferative forms and for assessing prognoses for LN.
We assessed the link between blood transcriptional signatures and LN using blood samples from patients with biopsy-proven LN, extra-renal SLE flares or quiescent SLE. Healthy controls, and control patients with glomerular diseases or bacterial sepsis were included. Modular repertoire analyses from microarray data were confirmed by PCR.
A modular neutrophil signature (upregulation of module M5.15) was present in 65% of SLE patients and was strongly associated with LN. M5.15 activity was stronger in LN than in extra-renal flares (88 vs 17%). M5.15 was neither correlated to IFN modules, nor to SLEDAI or anti-dsDNA antibodies, but moderately to CS dose. M5.15 activity was associated with severity of LN, was stronger when proliferative, and decreased in patients responding to treatment. M5.15 activation was not caused by higher CS dose because it correlated only moderately to neutrophil count and was also observed among quiescent patients. Among quiescent patients, those with a past history of LN had higher M5.15 activity (50 vs 8%). M5.15 activation was present in patients with bacterial sepsis or ANCA-associated vasculitis, but not in patients with other glomerular diseases. Overall, M5.15 activation was associated with past, present or future flares of LN.
Modular neutrophil signature could be a biomarker for stratifying LN risk and for monitoring its response to treatment.
ClinicalTrials.gov, http://clinicaltrials.gov , NCT00920114.
狼疮性肾炎（LN）是系统性红斑狼疮（SLE）的一种严重并发症。需要非侵入性生物标志物来识别有肾活动风险的患者，区分增殖性与非增殖性形式，并评估LN的预后。
我们使用经活检证实为LN、肾外SLE活动或静止期SLE患者的血样，评估血液转录特征与LN之间的联系。纳入了健康对照、患有肾小球疾病或细菌性败血症的对照患者。通过聚合酶链反应（PCR）证实了来自微阵列数据的模块化谱分析。
65%的SLE患者存在模块化中性粒细胞特征（模块M5.15上调），且与LN密切相关。M5.15活性在LN中比在肾外活动中更强（88%对17%）。M5.15既与干扰素模块无关，也与SLE疾病活动指数（SLEDAI）或抗双链DNA抗体无关，但与糖皮质激素（CS）剂量呈中度相关。M5.15活性与LN的严重程度相关，在增殖性LN中更强，在对治疗有反应的患者中降低。M5.15激活并非由更高的CS剂量引起，因为它仅与中性粒细胞计数呈中度相关，且在静止期患者中也有观察到。在静止期患者中，有LN既往史的患者M5.15活性更高（50%对8%）。M5.15激活在细菌性败血症或抗中性粒细胞胞浆抗体（ANCA）相关血管炎患者中存在，但在其他肾小球疾病患者中不存在。总体而言，M5.15激活与LN的既往、当前或未来活动相关。
模块化中性粒细胞特征可能是一种用于分层LN风险和监测其治疗反应的生物标志物。
ClinicalTrials.gov，http://clinicaltrials.gov ，NCT00920114 。
