Plasma level of lipocalin 2 is increased in neovascular age-related macular degeneration patients, particularly those with macular fibrosis.
Plasma level of lipocalin 2 is increased in neovascular age-related macular degeneration patients, particularly those with macular fibrosis.
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DOI：
10.1186/s12979-020-00205-w
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发表时间：
2020-11-14
期刊：
影响因子：
--
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Chen M;Yang N;Lechner J;Toth L;Hogg R;Silvestri G;Chakravarthy U;Xu H
以前，我们和其他人报道了新生血管性年龄相关性黄斑变性（nAMD）患者的循环中性粒细胞数量较高。中性粒细胞明胶酶相关脂质运载蛋白（NGAL，也称为脂质运载蛋白-2，LCN 2）是一种重要的先天性免疫介质，已知其与无菌炎症介导的器官衰竭、纤维化、癌症进展和视网膜变性密切相关。本研究调查了不同类型nAMD患者血浆LCN 2、基质金属蛋白酶9（MMP 9）和LCN 2/MMP 9复合物的水平，并检查了这些水平是否与患者对抗VEGF治疗的反应性相关。174例nAMD患者，包括108例脉络膜新生血管形成（CNV），32例视网膜血管瘤增生（RAP），23例息肉状脉络膜血管病变（PCV）和11例未分类患者，以及43例健康对照被招募到该病例对照研究中。58名nAMD患者有黄斑纤维化，110名患者没有。在174名nAMD患者中，80名患者对抗VEGF治疗完全应答，90名患者对抗VEGF治疗部分应答，4名患者对抗VEGF治疗无应答。nAMD患者血浆LCN 2水平（181.46 ± 73.62 ng/ml）显著高于健康对照组（152.24 ± 49.55 ng/ml，P = 0.047）。然而，在调整年龄后，这种差异消失了。nAMD患者血浆LCN 2水平与年龄呈正相关（r = 0.29，P = 0.0002），而健康对照组无相关性。在nAMD患者中，LCN 2的血浆水平也与循环中性粒细胞正相关（r = 0.34，p = 0.0007），但在健康对照中不相关（r = 0.057，p = 0.77）。年龄和循环中性粒细胞之间没有观察到相关性。对nAMD亚型的进一步分析发现，即使在调整年龄后，黄斑纤维化患者的LCN 2水平也显著较高。未观察到血浆LCN 2水平与患者对抗VEGF治疗的反应性之间的关系。nAMD与对照组血浆MMP 9和LCN 2/MMP 9复合物水平相当。我们的研究结果表明，nAMD中较高的LCN 2血浆水平与衰老和循环中性粒细胞数量增加有关。我们的研究结果还表明，较高水平的LCN 2可能会增加nAMD黄斑纤维化的风险。
Previously, we and others have reported higher populations of circulating neutrophils in patients with neovascular age-related macular degeneration (nAMD). Neutrophil gelatinase-associated lipocalin (NGAL, also known as lipocalin-2, LCN2), an important innate immune mediator, is known to be critically involved in sterile inflammation-mediated organ failure, fibrosis, cancer progression and retinal degeneration. This study investigated the plasma levels of LCN2, matrix metalloproteinase 9 (MMP9) and LCN2/MMP9 complex in different types of nAMD and examined whether the levels were related to patients’ responsiveness to anti-VEGF therapy. One hundred and seventy-four nAMD patients, including 108 with choroidal neovascularisation (CNV), 32 with retinal angiomatous proliferation (RAP), 23 with polypoidal choroidal vasculopathy (PCV) and 11 unclassified patients, and 43 healthy controls were recruited to this case-control study. Fifty-eight nAMD patients had macular fibrosis and 110 patients did not. Out of the 174 nAMD patients, 80 patients responded completely, 90 responded partially, and 4 did not respond to the anti-VEGF therapy. The plasma levels of LCN2 in nAMD patients (181.46 ± 73.62 ng/ml) was significantly higher than that in healthy controls (152.24 ± 49.55 ng/ml, P = 0.047). However, the difference disappeared after adjusting for age. A positive correlation between plasma level of LCN2 and age was observed in nAMD patients (r = 0.29, P = 0.0002) but not in healthy controls. The plasma level of LCN2 was also positively correlated with circulating neutrophils in nAMD patients (r = 0.34, p = 0.0007) but not in healthy controls (r = 0.057, p = 0.77). No correlation was observed between age and circulating neutrophils. Further analysis of nAMD subtypes uncovered a significantly higher level of LCN2 in patients with macular fibrosis even after adjusting for age. No relationship was observed between plasma levels of LCN2 and patients’ responsiveness to anti-VEGF therapy. The plasma levels of MMP9 and LCN2/MMP9 complex were comparable between nAMD and controls. Our results suggest that higher plasma levels of LCN2 in nAMD are related to ageing and increased population of circulating neutrophils. Our results also suggest that higher levels of LCN2 may increase the risk of macular fibrosis in nAMD.
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DOI：
10.1186/s12979-017-0100-9
发表时间：
2017
期刊：
Immunity & ageing : I & A
影响因子：
--
作者：
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Sørensen TL
DOI：
10.1002/path.4870
发表时间：
2017-04
期刊：
The Journal of pathology
影响因子：
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作者：
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Sinha D
DOI：
10.1186/s12979-016-0060-5
发表时间：
2016
期刊：
Immunity & ageing : I & A
影响因子：
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作者：
Lechner J;Chen M;Hogg RE;Toth L;Silvestri G;Chakravarthy U;Xu H
通讯作者：
Xu H
DOI：
10.1038/nri3459
发表时间：
2013-06
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
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DOI：
10.1212/nxi.0000000000000191
发表时间：
2016-02
期刊：
Neurology(R) neuroimmunology & neuroinflammation
影响因子：
--
作者：
Al Nimer F;Elliott C;Bergman J;Khademi M;Dring AM;Aeinehband S;Bergenheim T;Romme Christensen J;Sellebjerg F;Svenningsson A;Linington C;Olsson T;Piehl F
通讯作者：
Piehl F